#aminotransferases

[jcmicr]

Role of Alpha Fetoprotein in hepatocellular carcinoma by MuhammadWaqar Mazhar in Journal of Clinical and Medical Images, Case Reports 

Abstract

Hepatocellular carcinoma prevelance rate is higher in Pakistan due to HCV mortality rate, consumption of Alchol, and regular smoking, higher level of AFP progression normal liver cells into fatty liver cells, after inflammation it convert into HCC.In this study, we find the correlation between AFP and hepatocellular carcinoma. AFP involve in development of liver cancer, LFT’s test elevation and HCV also cause of cancer.

Keywords: Hepatocellular Carcinoma; Alpha Fetoprotein; alanine amino transferases; aspartate aminotransferases.

Introduction

Hepatocellular carcinoma is the 4th most common malignancy in worldwide and it is leading cause of cancer like disease in liver, and it exceed more than 1 million deaths per year by 2030 [1]. Acute hepatitis and acute liver failure are the most serious medical condition that require early diagnosis by release of IL-6, TNF-α and elevated alanine amino transferases, aspartate aminotransferases, alkaline phosphatase and α -Fetoprotein that progress healthy liver in to fatty liver known as steatosis and then inflammation occur in this and leads to hepatocellular carcinoma [2]. Most cases of HCC due to the virus like HCV and HBV, Diabetic and obesity, alcohol related diseases, non- alcohol related diseases, carcinogens like aflatoxins compounds [3]. HCC is the most common cancer that have high mortality rate in cancers due to mortality of HCV and NLFD. In Pakistan HCC ratio high due to prevalence and mortality rate of HCV [4]. The major treatment of HCC are chemotherapy, radiotherapy, transplantation and surgery. Because the most cases diagnose at the late stage, surgery cannot be performed and drugs are the only treatment of HCC [5]. Most patients in HCC become more drug resistance drug resistance. Drug treatment is the best choice of patients who are not edible for surgery. HCC is usually resistance to chemotherapeutic drugs. Because it hinders liver cancer treatment. In recent years targeted drugs use as medication and immune checkpoint inhibitors are introduce for treatment [6].

In the previous research evidence indicates that alpha-fetoprotein has high false-positive rate in diagnosis of early stage of HCC. The EASL clinic practices shows that AFP as a biomarker for liver transplantation and drug indicator [7]. The AFP level increased in many patients’ ad its risk for progression of HCC. AFP, currently the only biomarker available for HCC drug treatment, function as immune suppressor and promote malignancy transformation in HCC [8]. HCC is resistant to traditional chemotherapeutic agents such as doxorubicin, tetrahydrofolate, oxaliplatin, cisplatin, and gemcitabine. currently the recommended drugs include such as targeted therapeutics and immune checkpoint inhibitors [9].

AFP is a glycoprotein that secreted by endoderm embryonic tissue. The lower level of AFP in blood due to AFP is decrease in mature hepatocytes and that AFP gene expression is blocked. It is possible that AFP involved in HCC development and progression become an important factor affecting HCC diagnosis and treatment. AFP plays an important role in promoting cancer cell proliferation and, inhibition cancer cell apoptosis.

LFT’s test performed for liver injury, alanine aminotransferases, aspartate aminotransferases and alkaline phosphatase. These enzymes are commonly elevated in liver disease patients. Alkaline phosphatase and AFP play important role in the diagnosis of cancer.

Case Study

The patient name was sikandar, age 56 patient feel pain in their abdomen and sudden loss of weight. The patient has already hepatitis C infection and their PCR results were positive with high viral load. Due to serious illness it admitted in emergency ward 12, Nishter Hospital Multan. The doctors panel referred some test and kept in observations for better health condition.

The total bilirubin level was 2.05mg/dl in their blood and their normal values 0.6 - 1.2. The serum glutamate-pyruvate transaminase level is 43U/L and normal values up to 40. Aspartate amino transferases and alkaline phosphatase level were high in blood respectively 151 U/L and 493 U/l show in (Figure 1). Its indicate liver injury and cirrhosis. The AFP test indicates correlation with Hepatocellular carcinoma. The AFP level in patient was 6101ng/ml and normal values were 0.1 – 10. Higher level of AFP indicates that HCC have positive relation with AFP to proliferate cancer. The test formed by fully automated state of the Art analyzer Beckman Coulter 700 AIJ.

https://jcmimagescasereports.org/wp-content/uploads/2022/10/fig-1-10.jpg

Figure 1: Liver function and Alpha Feto Protein test in patient.

After blood reports, doctor suggest ultarosund Computrised Tomography whole abdominal view. In view, spleen size becomes enlarged 6cm, calculi in gall bladder, heterogeneous patchy atrial enhancement of right lobe, and some nodules seen in both lobes of liver. The doctor findings the AFP correlation with HCC, splenomegaly, ascites, cholelithiasis and protosystematic collaterals.

https://jcmimagescasereports.org/wp-content/uploads/2022/10/fig-2-10.jpg

Figure 2: Ultrasound Computrised Tomography whole abdomen.

The patient diagnosed with hepatocellular carcinoma at last stage, and doctor reffered to liver transplantation in india. But after 4 weeks he cannot survive.

Conclusion

Hepatitis C was the major risk of hepatocellular carcinoma in Pakistan. Smoking and alcohol have big problem to influence HCC in humans. The case study show that alpha fetoprotein has correlation with HCC. Higher Alkaline phosphatase and serum Bilirubin level enhance the liver carcinoma. AFP play role in cell proliferation, cancer cell differentiation and cell cycle arrest.

For more details : https://jcmimagescasereports.org/author-guidelines/ 

[orangemocharaktajino]

he ain't wrong

[girlyblunts]

My doctor thinks that I have gastroparesis, and I’m waiting for so many blood work results but my A1C levels are pre-diabetic :-)

[healixhospitals24]

Learn to interpret your liver function test results with our comprehensive guide. Understand commonly used liver tests and their implications for your health.

Do Visit: https://www.healixhospitals.com/blogs/reading-and-interpreting-your-liver-function-test-a-guide-to-commonly-used-liver-tests

[harmeet-saggi]

Understanding Liver Function Test

What is a liver function test?

A liver function test is a blood test that measures the levels of various enzymes and proteins in your blood. These substances are produced by the liver, and they can be a sign of liver damage or disease.

[jcrmhscasereports]

Case of Necrotizing Pancreatitis following COVID-19 Infection by Faezeh Sehatpour in Journal of Clinical Case Reports Medical Images and Health Sciences  

ABSTRACT

New aspects of COVID-19 are increasingly being recognized. Although the virus is mainly known to affect the lungs, involvement of other organs including the heart, liver, gastrointestinal, renal and pancreas is also detected. Acute pancreatitis is detected as one of both the early and late presentations of COVID -19. Cytokine storm or the presence of angiotensin-converting enzyme 2 (ACE2) receptor in pancreatic cells, are both two causes of pancreatic injury in COVID-19 infection. In this study, we reported a 25-year-old man admitted to our department with the impression of necrotizing pancreatitis concomitant with COVID-19 infection. Patient's lab data, imaging and outcomes were documented in full detail.

Abbreviations:

WBC, white blood cell;HB, hemoglobin; MCV, mean corpuscular volume; PLT, platelet; BUN, blood urea nitrogen; Na, sodium; K, potassium; ; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALK.P, alkaline phosphatase; ALB, albumin; LDH, Lactate dehydrogenase ; CPK, creatine phosphokinase; CRP,c-reactive protein; AFP,alpha-fetoprotein; CEA,carcinoembryonic antigen; CA19-9,cancer antigen 19-9; Immunoglobulin G4.

INTRODUCTION

The Covid-19 pandemic is an ongoing pandemic that started in December 2019 and spread rapidly around the word. COVID-19 was caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), first identified in Wuhan, China. So far, more than 200 countries have been affected by the pandemic. (1)

New aspects of COVID-19 are increasingly being recognized. Although the virus is mainly known to affect the lungs, involvement of other organs including the heart, liver, gastrointestinal, renal and pancreas is increasingly being reported. (2)

The involvement of the gastrointestinal system is maybe due to the expression of the angiotensin-converting enzyme2 (ACE2) on the hepatocyte, cholangiocyte and  other parts of the GI tract. (3) In a recent survey, acute pancreatitis was detected as one of both early and late presentations of COVID -19. (4-6) However, it is still unclear whether SARS-COV-2 directly affects pancreatic cells because of ACE2, if it is a cytokine storm which causes pancreatic injury. (7)

We reported a case of COVID-19 with subsequent acute necrotizing pancreatitis.

CASE REPORT

A 25-year-old man without any known medical disease presented to our emergency department with progressive epigastric pain, nausea and vomiting and anorexia one week prior to admission. He has no history of alcohol consumption. He also had a history of admission to another hospital about two weeks ago with a diagnosis of COVID-19 pneumonia. On admission, he has a blood pressure of 115/75 mm HG, a heart rate of 100 beats per minute, a temperature of 37.1 ⁰C and oxygen saturation of 95% while the patient is breathing in the room air. Primary investigations summarized in Table-1. Amylase and lipase were 146 IU/L and 82 IU/L respectively. Nasal swab test for COVID-19 (RT-PCR for SARS-CoV-2) was positive. Abdominal sonography showed markedly prominent pancreas with in homogeneous parenchymal echogenicity and large cystic lesion arising from the pancreas, in favor of acute complicated pancreatitis with pseudo cyst. The gall bladder has a normal size and wall thickness without any gall stones. The pancreatic duct was not dilated.  Due to the finding of abdominal ultra sound, CT scan of abdomen was done on him which revealed an enlarged pancreas with necrosis of the main portion of pancreatic parenchyma. Large cystic lesion measuring 15×7×11 cm in size arising from the pancreatic neck with extension to the right and left side of the abdomen suggestive of large pancreatic pseudo cyst (figure1).  Lung HRCT (low dose) also showed bilateral peripheral ground glass opacities in favor of COVID-19 pneumonia (figure2). According to the findings of a physical exam, laboratory data and clues in imaging immediate management of acute necrotizing pancreatitis (invasive intravenous hydration and pain control) was started for him. He was finally discharged from the hospital with a full recovery.

Table 1: laboratory data

Figure 1: Abdominal CT scan:  large loculated pseudo cystic structure measuring about 158mm*100mm in lesser sac due to post pancreatitis pseudo cyst formation.

Figure 2: lung HRCT: multiple ground glass and bilateral pleural effusion

DISCUSSION

Acute pancreatitis is an acute inflammation of the pancreas characterized by abdominal pain, nausea, vomiting and elevated exocrine pancreatic enzymes; amylase and lipase. Gallstones and chronic alcohol abuse are the most common causes of acute pancreatitis. Viruses are uncommon causes of acute pancreatitis. Pancreatitis has been reported with several viruses, including mumps, coxsackievirus, hepatitis A and B virus, cytomegalovirus, varicella-zoster, herpes simplex and human immunodeficiency virus. (8)

Although we have not conclusively proven the presence of the virus in the pancreas, the causes of COVID-19 and acute pancreatitis and the lack of other clear causes for pancreatitis strengthen the relationship between the two diseases.  In this study, the patient presented with necrotizing COVID-19in 19 in the early post period of COVID-19 infection.

In Fan Wang and colleagues' survey, 52 COVID-19 cases followed and showed that 17% of COVID-19 patients developed pancreatic injury and presented with mild elevated pancreatic enzymes; serum amylase and lipase without clinically severe pancreatitis. The possibility of drug induced acute pancreatitis in patients who have received medication due to COVID-19 is also expressed as one of the reasons for acute pancreatitis in COVID-for19 infection. (9) Saffa Saeed Al Mazrouei and his teammates reported a 24-year-old patient with acute non-necrotizing pancreatitis with concurrent COVID-19. No evidence of pseudo cyst or abscess was detected in his imaging. (10)

Pancreatic damage can be due to the direct effect of the virus on pancreatic cells or indirectly secondary to the immune system. In another study in Wuhan, it showed that ACE2 was expressed in the pancreas higher than the lung in the normal population, indicating that SARS-CoV-2 can bind to ACE2 in the pancreas and cause pancreatic cell damage. (7, 11)

Acute pancreatitis is one of the presentations or complications of COVID-19 infection. Further investigation with samples is needed to reveal the pathophysiology, presentation, treatment and prognosis of acute pancreatitis in COVID-19 infection.

For more information: https://jmedcasereportsimages.org/about-us/

For more submission : https://jmedcasereportsimages.org/

[tenth-sentence]

The aminotransferases in chloroplasts may have a significant role in amino acid biosynthesis, because plant leaves or isolated chloroplasts exposed to radioactively labeled carbon dioxide rapidly incorporate the label into glutamate, aspartate, alanine, serine, and glycine.

"Plant Physiology and Development" int'l 6e - Taiz, L., Zeiger, E., Møller, I.M., Murphy, A.

[genderqueerdykes]

usa based anon trans masc (who has been on T for 7 years): the tests my doc ordered for last year's check were: lipid panel, testosterone total, hemoglobin, hemoglobin a1c, hemocrit, estradiol, asparatane aminotransferase, and alanine aminotransferase. from there you can look up the average values of these results, and maybe check it against your prev tests before hrt.

thank you so much holy shit!

[primamedikatama]

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[jcmicr]

Role of Alpha Fetoprotein in hepatocellular carcinoma by MuhammadWaqar Mazhar in Journal of Clinical and Medical Images, Case Reports  

Abstract

Hepatocellular carcinoma prevelance rate is higher in Pakistan due to HCV mortality rate, consumption of Alchol, and regular smoking, higher level of AFP progression normal liver cells into fatty liver cells, after inflammation it convert into HCC.In this study, we find the correlation between AFP and hepatocellular carcinoma. AFP involve in development of liver cancer, LFT’s test elevation and HCV also cause of cancer.

Keywords: Hepatocellular Carcinoma; Alpha Fetoprotein; alanine amino transferases; aspartate aminotransferases.

Introduction

Hepatocellular carcinoma is the 4th most common malignancy in worldwide and it is leading cause of cancer like disease in liver, and it exceed more than 1 million deaths per year by 2030 [1]. Acute hepatitis and acute liver failure are the most serious medical condition that require early diagnosis by release of IL-6, TNF-α and elevated alanine amino transferases, aspartate aminotransferases, alkaline phosphatase and α -Fetoprotein that progress healthy liver in to fatty liver known as steatosis and then inflammation occur in this and leads to hepatocellular carcinoma [2]. Most cases of HCC due to the virus like HCV and HBV, Diabetic and obesity, alcohol related diseases, non- alcohol related diseases, carcinogens like aflatoxins compounds [3]. HCC is the most common cancer that have high mortality rate in cancers due to mortality of HCV and NLFD. In Pakistan HCC ratio high due to prevalence and mortality rate of HCV [4]. The major treatment of HCC are chemotherapy, radiotherapy, transplantation and surgery. Because the most cases diagnose at the late stage, surgery cannot be performed and drugs are the only treatment of HCC [5]. Most patients in HCC become more drug resistance drug resistance. Drug treatment is the best choice of patients who are not edible for surgery. HCC is usually resistance to chemotherapeutic drugs. Because it hinders liver cancer treatment. In recent years targeted drugs use as medication and immune checkpoint inhibitors are introduce for treatment [6].

In the previous research evidence indicates that alpha-fetoprotein has high false-positive rate in diagnosis of early stage of HCC. The EASL clinic practices shows that AFP as a biomarker for liver transplantation and drug indicator [7]. The AFP level increased in many patients’ ad its risk for progression of HCC. AFP, currently the only biomarker available for HCC drug treatment, function as immune suppressor and promote malignancy transformation in HCC [8]. HCC is resistant to traditional chemotherapeutic agents such as doxorubicin, tetrahydrofolate, oxaliplatin, cisplatin, and gemcitabine. currently the recommended drugs include such as targeted therapeutics and immune checkpoint inhibitors [9].

AFP is a glycoprotein that secreted by endoderm embryonic tissue. The lower level of AFP in blood due to AFP is decrease in mature hepatocytes and that AFP gene expression is blocked. It is possible that AFP involved in HCC development and progression become an important factor affecting HCC diagnosis and treatment. AFP plays an important role in promoting cancer cell proliferation and, inhibition cancer cell apoptosis.

LFT’s test performed for liver injury, alanine aminotransferases, aspartate aminotransferases and alkaline phosphatase. These enzymes are commonly elevated in liver disease patients. Alkaline phosphatase and AFP play important role in the diagnosis of cancer.

Case Study

The patient name was sikandar, age 56 patient feel pain in their abdomen and sudden loss of weight. The patient has already hepatitis C infection and their PCR results were positive with high viral load. Due to serious illness it admitted in emergency ward 12, Nishter Hospital Multan. The doctors panel referred some test and kept in observations for better health condition.

The total bilirubin level was 2.05mg/dl in their blood and their normal values 0.6 - 1.2. The serum glutamate-pyruvate transaminase level is 43U/L and normal values up to 40. Aspartate amino transferases and alkaline phosphatase level were high in blood respectively 151 U/L and 493 U/l show in (Figure 1). Its indicate liver injury and cirrhosis. The AFP test indicates correlation with Hepatocellular carcinoma. The AFP level in patient was 6101ng/ml and normal values were 0.1 – 10. Higher level of AFP indicates that HCC have positive relation with AFP to proliferate cancer. The test formed by fully automated state of the Art analyzer Beckman Coulter 700 AIJ.

Figure 1: Liver function and Alpha Feto Protein test in patient.

After blood reports, doctor suggest ultarosund Computrised Tomography whole abdominal view. In view, spleen size becomes enlarged 6cm, calculi in gall bladder, heterogeneous patchy atrial enhancement of right lobe, and some nodules seen in both lobes of liver. The doctor findings the AFP correlation with HCC, splenomegaly, ascites, cholelithiasis and protosystematic collaterals.

Figure 2: Ultrasound Computrised Tomography whole abdomen.

The patient diagnosed with hepatocellular carcinoma at last stage, and doctor reffered to liver transplantation in india. But after 4 weeks he cannot survive.

Conclusion

Hepatitis C was the major risk of hepatocellular carcinoma in Pakistan. Smoking and alcohol have big problem to influence HCC in humans. The case study show that alpha fetoprotein has correlation with HCC. Higher Alkaline phosphatase and serum Bilirubin level enhance the liver carcinoma. AFP play role in cell proliferation, cancer cell differentiation and cell cycle arrest.

For more details : https://jcmimagescasereports.org/author-guidelines/ 

[jcsmicasereports]

Acute kidney injury following exposure to a formaldehyde –free hair straightening products by Dr. Nabil Abu-Amer in Journal of Clinical Case Reports Medical Images and Health Sciences

ABSTRACT

Formaldehyde- free hair straightening products are hair smoothening solutions widely used by professional beauty salons. Formaldehyde-free hair straighteners do not technically contain formaldehyde, however they contain other chemicals such as glyoxyloyl carbocysteine which releases formaldehyde upon contact with heat. Moreover, its by-product glyoxylate may convert to oxalate, both compounds have potential nephrotoxic effect.

Case presentation: 41-year-old woman presented to the emergency room with weakness, nausea , vomiting and  stage three acute kidney injury according to Kidney Disease: Improving Global Outcomes acute kidney injury staging (KDIGO) shortly after exposure to formaldehyde - free hair straightening product, other causes of acute kidney injury were excluded such as preceding acute illness, drug history or others nephrotoxic agent exposure On physical examination the patient was pale, her vital signs were normal. The urine microscopy and serologic workup was not indicative. Kidney core biopsy reveal interstitial edema, acute interstitial nephritis and oxalate crystal nephropathy. Kidney function completely recovered after a short course of steroid therapy.

Conclusions: We present a case of severe kidney injury after exposure to hair straightening products branded as formaldehyde free but actually contain other chemicals products which release formaldehyde and other toxic chemicals when heated during the straightening procedure and  may cause systemic toxicity, particularly kidney injury. Different cosmetic products are widely in use, not all are under a tight regulation, and therefore it is important to raise the awareness of both medical teams and consumers of possible adverse health effects of different cosmetic products.

INTRODUCTION

Nephrotoxicity is defined as kidney injury due to toxic effects of chemicals. There are various forms of chemicals and drugs that may affect renal function in various mechanism including acute tubular necrosis (ATN), tubulopathy and electrolyte imbalance, acute interstitial nephritis (AIN), glomerular damage, crystal nephropathy, and thrombotic microangiopathy [1-3].

Formaldehyde- free hair straightening products contain potentially toxic chemicals other than formaldehyde. One potential such substance is glyoxyloyl carbocysteine, which is composed of glyoxylic acid, cysteine and acetic acid. Glyoxylic acid both releases formaldehyde when heated and is converted into either glycine by AGT1 (alanine:glyoxylate aminotransferase 1) or oxalate by glycolate oxidase in the human cell peroxisomes [4].

Formaldehyde is a colorless aldehyde poisonous gas at room temperature [5]. It is usually mixed with water and when the small fraction of soluble formaldehyde reacts with water, it quickly forms methylene glycol. For every molecule of free formaldehyde, 1,820 molecules of methylene glycol are formed [6]. Methylene glycol reverts back to free formaldehyde almost immediately upon contact with air or skin. Formaldehyde is thus absorbed through skin, eyes, and inhalation, and is eliminated through the urine [7-8]. During the hair straightening process, high levels of formaldehyde are found in samples of air taken from beauty salons [9] and in specimens of hairstylist workers skin [10-11].

In the kidney, formaldehyde has been reported to cause direct cytotoxic effect resulting in acute toxic tubular necrosis [12-13], and may also cause an immune system response leading to acute interstitial nephritis.

Another potential nephrotoxic component of hair straightening products is oxalate, which is an end product of glyoxylic acid.  Increased levels of oxalate promote calcium oxalate precipitation in various tissues including the kidneys, resulting in toxic injury.

Case presentation

A 41-year-old woman with a history of hypothyroidism and sleeve gastrectomy five years ago, presented to the emergency department with profound weakness, nausea and vomiting. Her symptoms began three days earlier, immediately after using a professional hair straightening formaldehyde- free product in a professional beauty salon.

On physical examination the patient was pale, her vital signs were normal, heart rate  was 66 bpm, blood pressure was 125/70 mmHg, she had no fever or respiratory distress and appeared euvolemic.

Laboratory investigations revealed a serum creatinine of 3.46 mg/dl (one year prior to the event Cr. value was 0.6 mg/dl), urea 77 mg/dl, and electrolytes, liver function tests, Beta human chorionic gonadotropin (β-hCG) and complete blood count were normal. Blood venous gases revealed: pH 7.375, HCO3 21 mmol/L and base excess 3 mmol. The anion gap and serum osmolar gap were normal. Urinalysis demonstrated leukocyturia +1 without hematuria or proteinuria.

During hospitalization urine output was normal, repeat urinalysis demonstrated leukocyturia +1 without hematuria or proteinuria, and Bence-Jones protein was negative. Urine microscopy demonstrated epithelial cells with few white blood cells without any casts or crystals. Renal ultrasound showed 14.4 cm bilateral echogenic, edematous renal parenchyma (shown in  Fig. 1).

A full serologic workup including hepatitis B and C, Human immunodeficiency virus (HIV), syphilis, antinuclear antibody (ANA) , Anti-double stranded DNA, Antineutrophil cytoplasmic antibody (ANCA), Anti-Phospolipid antibody (APLA) was normal except for a complement C3 level of 80 mg/dl (normal range 90-110 mg/dl).

On the 4th hospitalization day a renal core biopsy was performed. The histologic examination (shown in Fig. 2) was correlatd with  acute tubular necrosis, tubulo- intersitial nephritis and oxalate crystals . With the diagnosis of interstitial nephritis, the patient was started on prednisolone 1 mg/kg, one week later serum creatinine decreased to a level of 0.98 mg/dl.

A: Glomeruli were normo-cellular and without signs of active glomerular disease (arrow heads), tubules showed signs of diffuse tubular injury (black arrow) and tubules contained oxalate crystals (blue arrow). B:The interstitium showed edema associated with multifocal mixed inflammatory infiltration with multiple eosinophils and foci of tubulitis. C:There was one epithelioid granuloma. D:Tubules contained oxalate crystals (blue arrow) observed under polarized light-microscopy. Immunofluorescence analysis revealed C3 1+ in blood vessel walls only.

Discussion

This patient presents an unusual case of kidney toxic and inflammatory injury accompanied with oxalate deposition secondary to hair straightening product. In a literature review, only few cases [14-15] of acute kidney injury (AKI) following hair straightening formaldehyde- free product exposure were reported. All cases were reported after 2019. The spectrum of kidney injury following hair straightening ranges from mild to severe kidney injury requiring renal replacement therapy. The histopathologic changes reported mainly depicted severe acute tubular necrosis and acute interstitial nephritis.

Our patient presented with stage 3 AKI following hair straightening formaldehyde - free product exposure. Other causes of AKI were excluded such as preceding acute illness, drug history or other nephrotoxic agent exposure. Laboratory workup revealed leukocyturia +1, and ultrasonography was significant for enlarged edematous echogenic renal parenchyma. Kidney biopsy demonstrated acute interstitial nephritis, oxalate crystal precipitation and acute tubular necrosis. We speculate that the clinical presentation and the histopathologic changes directly resulted from exposure to the hair straightening formaldehyde- free product.

In reviewing the ingredients of the specific product used in this case, it included glyoxyloyl carbocysteine, glyoxyloyl keratin amino acid, propylene glycol glycerin, phenoxyethanol, ethylhexylglycerin disodium and other collagen, surfactant and fragrance components. We did not find evidence in the medical, pharmacological and chemical literature that any of these substances causes acute kidney injury other than glyoxyloyl carbocysteine.

Many hair straightening products are labeled as formaldehyde "free" but actually contain chemicals such as glyoxyloyl carbocysteine or methylene glycol which release formaldehyde and other toxic chemicals when heated, e.g the carbocysteine hair treatment represents the combination of glyoxylic acid + cisteine + acetic acid. Glyoxylic acid contains an aldehyde functional group, glyoxylic acid behaves as an aldehyde by  heating during the hair straightening process thus releasing high levels of formaldehyde gas exceeding the capacity of exposure[16]. On top of that, glyoxylic acid absorbed through the scalp may had converted to oxalic acid [17] which may precipitate in kidney tissue. It is possible that other components such as propylene glycol may cause osmotic renal injury. In this case, serum osmotic gap was not available since it calculated four days after exposure.

Conclusion

In conclusion, a case of severe kidney injury after exposure to hair straightening products branded as formaldehyde free is presented. This case highlights the sensitivity of the kidney to various environmental and commercial products, some of which have not been fully characterized or identified yet.

It is important to raise the awareness of both medical teams and consumers, of possible adverse health effects of different cosmetic products, including acute kidney injury, and perhaps promote tighter regulation of such products.

Statement of Ethics:

Ethical approval is not required for this study in accordance with local or national guidelines.

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available.

Conflict of Interest interests

The authors have no conflict of interest to disclose

Funding

No funding was obtained for this study.

Authors’ contributions

NAA, NZ, SM, PB, were involved in the clinical management of the patient.

NAA, MK, collected the data and wrote the first version of the manuscript.

NAA, NZ, MK, SM, PB approved the final version of the manuscript.

The authors read and approved the final manuscript.

Data Availability

All data that support the findings of this study are included in this article.

[helen0086]

Progress in the Study of the Protective Effect and Mechanism of C-phycocyanin on Liver Injury

Abstract: C-phycocyanin (C-phycocyanin) is a pigment-containing protein from marine algae that has shown promising results in the treatment of many inflammatory diseases and tumors. C-alpha-cyanobilin is a pigment-containing protein from marine algae that has been shown to be effective in the treatment of various inflammatory diseases and tumors. C-alpha-cyanobilin has a protective effect on various liver diseases, such as drug-induced or toxic substance-induced liver damage, non-alcoholic fatty liver disease, hepatic fibrosis, and hepatic ischemia-reperfusion injury. The protective effect of C-alginin on liver injury is mainly realized through the regulation of signaling pathways such as nuclear factor (NF)-κB, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and AMP-dependent protein kinase (AMPK), and the inhibition of oxidative stress, etc., and is not toxic to normal cells. Therefore, C-alginin has a broad application prospect as a potential natural hepatoprotective marine active substance. In recent years, the research progress of the protective effect of C-alginin on liver injury and its mechanism is summarized.

 C-phycocyanin (C-phycocyanin) is a complex protein of cyanobacteria and a natural food protein pigment with pharmacological effects such as antioxidant, anti-inflammatory and anti-tumor effects, as well as fast-acting and low-toxicity, it can be used as a functional food [1-2]. C-Alginin can also enhance immunity and is safe, without causing acute and subacute toxic reactions [3]. Selenium-enriched PC has been shown to have stronger pharmacological effects [4]. Therefore, C-alginate has important research value both as a drug and a functional food, and has become a hot spot in the field of pharmaceutical research [5]. In this paper, we summarize the progress of research on the application and mechanism of C-alginin in liver diseases.

1 Ameliorative effect of C-phycocyanin on liver injury caused by drugs and toxic substances

The liver is the metabolic center of drugs and exogenous toxic substances, and metabolites are prone to liver injury. C-PC can inhibit the synthesis and release of inflammatory factors such as tumor necrosis factor (TNF)-α and interferon-γ, and increase the activities of catalase and superoxide dismutase (SOD), which can inhibit hepatic inflammation and alleviate hepatic injury [3]. It has been found that C-PC can significantly prevent thioacetamide-induced liver injury, significantly reduce the levels of alanine aminotransferase (ALT) and aliquot aminotransferase (AST), shorten the prothrombin time and reduce the hepatic histopathological damage, and improve the survival rate of rats with fulminant hepatic failure [6]. C-alginin also has a good effect on thioacetamide-induced hepatic encephalopathy, which can be seen in the reduction of tryptophan and lipid peroxidation indexes in different regions of the brain, and the enhancement of catalase and glutathione peroxidase activities in rats with fulminant hepatic failure [6].

Another study found that C-alginin not only attenuates the oxidative stress induced by 2-acetylaminofluorene and reduces the generation of reactive oxygen species (ROS) radicals, but also inhibits the phosphorylation of protein kinase B (Akt) and the nuclear translocation of nuclear factor (NF)-κB induced by 2-acetylaminofluorene, thus inhibiting the expression of multidrug resistance genes [7]. Osman et al. [8] also showed that C-alginin could normalize the levels of ALT, AST, catalase, urea, creatinine, SOD and glutathione-s-transferase in the livers of rats poisoned with carbon tetrachloride (CCl4). This result was also verified in human liver cell line (L02) [9]. C-phycocyanin can effectively scavenge ROS and inhibit CCl4-induced lipid peroxidation in rat liver [10], and C-PC can improve the antioxidant defense system and restore the structure of hepatocytes and hepatic enzymes in the liver of gibberellic acid-poisoned albino rats [11]. As a PC chromophore, phycocyanin can also significantly inhibit ROS generation and improve liver injury induced by a variety of drugs and toxic substances [10]. Liu et al. [12] found that phycocyanin showed strong anti-inflammatory effects in a CCl4-induced hepatic injury model in mice, which could significantly reduce the levels of ALT, AST, the expression of TNF-α and cytochrome C, increase the levels of albumin and SOD, and proliferate cytosolic nuclei. It can significantly reduce ALT and AST levels and the expression of TNF-α and cytochrome C, increase albumin levels and the expression of SOD and proliferating cell nuclear antigen, promote hepatocyte regeneration and improve the survival rate of mice with acute liver failure.

Gammoudi et al [13] used response surface method to optimize the extraction process of C-phycocyanin, and obtained high extraction recovery. C-phycocyanin extracted by the optimized method has the ability of scavenging hydroxyl, superoxide anion and nitric oxide radicals as well as the ability of metal chelating, and it has stronger antioxidant effect; C-PC significantly increased the activity of SOD and inhibited the increase of ALT, AST, and bilirubin in cadmium-poisoned rats. C-PC significantly increased the activity of SOD and inhibited the increase of ALT, AST and bilirubin in rats with cadmium poisoning. The above studies show that C-phycocyanin can effectively protect liver injury caused by drugs and toxic substances, and has the efficacy as the basis for drug development.

2 Preventive effect of C-alginin on hepatic fibrosis

Liver fibrosis is an inevitable process in the development of various chronic liver diseases and may be reversed with early and timely treatment. The key to liver fibrosis is the activation of hepatic stellate cells. Previous studies have found that low-dose C-alginin combined with soy isoflavones can inhibit hepatic stellate cell activation by inhibiting the activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase［14］, but it is not clear whether C-alginin alone can inhibit the activity of NADPH oxidase. Therefore, the combination of C-algin and soy isoflavones at appropriate doses may have a preventive effect on liver fibrosis in high-risk groups. C-alginin may inhibit the progression of NADPH by suppressing oxidative damage, thereby inhibiting the development of hepatic fibrosis [15].

Epithelial mesenchymal transition (EMT) is one of the key mechanisms contributing to the development of fibrotic diseases. C-alginin inhibits transforming growth factor β1 (TGF-β1)-induced human EMT [16]. Although the effect of C-alginin on EMT in hepatic fibrosis has not been reported, it has been found that C-alginin can reduce pulmonary fibrosis by inhibiting epithelial mesenchymal transition [17]. Another study found that C-alginin could reduce the expression of α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) mRNA in human dermal fibroblasts and alleviate fibrous contracture [18]. The results of these studies also have significance for the inhibition of hepatic fibrosis, and provide a theoretical basis for the further study of C-PC as a potential antifibrotic drug.

3 Protective effect of C-alginin on hepatic ischemia-reperfusion injury

Liver ischemia/reperfusion injury is an important clinicopathophysiological phenomenon. It was found that the addition of two different doses (0.1 g/L and 0.2 g/L) of C-alginin to the Krebs Henseleit preservation solution significantly decreased hepatic ALT, AST and alkaline phosphatase activities, and reduced the rate of lipid peroxidation and malondialdehyde content in an isolated perfused rat liver model, and increased the activities of hepatic glutathione-s-transferase and glutathione peroxidase, as well as sulfhydryl groups in hepatic tissue. On the other hand, it can increase the activities of hepatic glutathione-s-transferase and glutathione peroxidase and the content of sulfhydryl groups in liver tissues, therefore, C-alginin can significantly reduce hepatic ischemia/reperfusion injury as an antioxidant [19]. In isolated perfused mouse livers, it was found that C-alginin significantly reduced the phagocytosis and respiratory burst activity of hepatic macrophages (Kupffer cells), attenuated cytotoxicity and inflammation induced by highly active Kupffer cells, and dose-dependently inhibited carbon phagocytosis and carbon-induced oxygen uptake by perfused livers, and then inhibited the increase of hepatic nitric oxide synthase activity induced by gonadotropins [20]. and thus inhibit the thyroid hormone-induced elevation of hepatic nitric oxide synthase activity [20].

However, C-alginin has a very short half-life in vivo, which limits its application in vivo. It was found that the use of polyethylene glycol-b-(polyglutamic acid-g-polyethyleneimine), a macromolecular material with good drug-carrying capacity and slow-release properties, as a nanocarrier of C-alginin could solve this problem, and the release of C-alginin could be delayed by subcutaneous injection into the abdominal region of rats, which could attenuate islet damage caused by hepatic ischemia/reperfusion and enhance the function of the islets [21]. This study broadens the scope of application of C-alginin in vivo and improves the therapeutic effect of C-alginin.

4 Inhibitory effect of C-alginin on hepatocellular carcinoma

It was found that C-alginin significantly reduced the expression of matrix metalloproteinase (MMP)-2 and MMP-9 and the expression of tissue inhibitor of metalloproteinase 2 (TIMP2) mRNA in human hepatocellular carcinoma cells (HepG2 cells) [22]. C-alginin is a natural photosensitizer, and photodynamic therapy (PDT) mediated by alginin microcystin induced a large accumulation of ROS in HepG2 cells, which promoted mitochondrial damage and cytochrome C release, and led to apoptosis of hepatocellular carcinoma cells [23].

Liu et al. [24] used nanoscale C-alginate particles prepared by lactobionic acid grafting and adriamycin loading to enhance the growth inhibition of HepG2 cells when combined with chemo-PDT, and the C-alginate particles could effectively accumulate and diffuse in tumor multicellular spheres. In vitro and in vivo studies on the effects of selenium-enriched PCs on PDT in hepatocellular carcinoma showed that selenium-enriched PCs could migrate from lysosomes to mitochondria in a time-dependent manner, and that selenium-enriched PCs could induce the death of tumor cells through the generation of free radicals in vivo, increase the activities of antioxidant enzymes in vivo, induce mitochondria-mediated apoptosis, and inhibit autophagy, thus offering a relatively safe pathway to tumor treatment and showing new development perspectives [4]. It can provide a relatively safe way to treat tumors and shows a new development prospect [4].

Lin et al. [25] combined C-phycocyanin with single-walled carbon nanohorns and prepared phycocyanin-functionalized single-walled carbon nanohorn hybrids, which enhanced the photostability of C-phycocyanin and protected the single-walled carbon nanohorns from adsorption of plasma proteins, and synergistically used with PDT and photothermal therapy (PTT) to treat tumors. C-phycocyanin covalently coupled with biosilica and PDT or non-covalently coupled with indocyanine green and PTT on tumor-associated macrophages can also increase the apoptosis rate of tumor cells [26-27]. The development of PDT and PTT synergistic methods for the treatment of cancer has broadened the application of C-PC and enhanced its value in the treatment of hepatocellular carcinoma.

In addition, C-phycocyanin can inhibit the expression of multidrug-resistant genes in HepG2 cells through NF-κB and activated protein-1 (AP-1)-mediated pathways, and C-phycocyanin increases the accumulation of adriamycin in HepG2 cells in a dose-dependent manner, which results in a 5-fold increase in the susceptibility of cells to adriamycin [28]. Even in adriamycin-resistant HepG2 cells, C-PC induced the activation of apoptotic pathways such as cytochrome C and caspase-3 [29], and the results of Prabakaran et al. [30] also confirmed the inhibitory effect of C-PC on the proliferation of HepG2 cells, mediated by the inactivation of BCR-ABL signaling and the downstream PI3K/Akt pathway. mediated by BCR-ABL signaling and inactivation of downstream PI3K/Akt pathway. In addition, C-phycocyanin modifies the mitochondrial membrane potential and promotes apoptosis in cancer cells [30]. Currently, C-phycocyanin is a synergistic molecule with other drugs that have been widely used in the treatment of cancer [31]. The above studies demonstrate that C-phycocyanin has good therapeutic potential in the field of hepatocellular carcinoma.

5 Amelioration of metabolic syndrome and non-alcoholic fatty liver disease by C-phycocyanin

It has been found that C-alginin can reduce ALT and AST levels, decrease ROS production and NF-κB activation, and attenuate hepatic fibrosis in rats induced by high-fat choline-deficient diets, and thus C-alginin has a protective effect on NAFLD rats through anti-inflammatory and antioxidant mechanisms [15].

Another study on the effects of aqueous extract of Spirulina (mainly C-alginin) on NAFLD induced by a high-calorie/high-fat Western diet in C57Bl/6J mice showed that aqueous extract of Spirulina significantly improved glucose tolerance, lowered plasma cholesterol, and increased ursodeoxycholic acid in bile in mice [32]. Kaspi-Chadli et al. Kasbi-Chadli et al. [33] showed that aqueous extract of Spirulina could reduce cholesterol and sphingolipid levels in the liver and aortic cholesterol levels in hamsters fed a high-fat diet by significantly decreasing the expression of hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA) gene, a limiting enzyme for cholesterol synthesis, and TGF-β1 gene, and that ursodeoxycholic acid levels in the feces of hamsters fed high-fat diets were increased in the high Spirulina aqueous extract treatment group.

A daily dose of C-alginin-enriched Spirulina can reduce the harmful effects of oxidative stress induced by a diet rich in lipid peroxides [34]. Ma et al. [35] found that C-alginin promoted the phosphorylation of hepatocyte AMP-dependent protein kinase (AMPK) in vivo and ex vivo, and increased the phosphorylation of acetyl coenzyme A carboxylase. In the treatment of NAFLD in mice, C-alginin can improve liver inflammation by up-regulating the expression of phosphorylated AMPK and AMPK-regulated transcription factor peroxisome proliferator-activated receptor α (PPAR-α) and its target gene, CPT1, and by down-regulating the expression of pro-inflammatory factors such as TNF-α and CD36 [35]. This suggests that C-phycocyanin can also improve lipid deposition in the liver through the AMPK pathway.

Endothelial dysfunction is associated with hypertension, atherosclerosis and metabolic syndrome. Studies in animal models of spontaneous hypertension have shown that long-term administration of C-alginin may improve systemic blood pressure in rats by increasing aortic endothelial nitric oxide synthase levels, with a dose-dependent decrease in blood pressure, and thus C-alginin may be useful in preventing endothelial dysfunction-related diseases in the metabolic syndrome [36]. In the offspring of ApoE-deficient mice fed C-alginate during gestation and lactation, male littermates had an elevated hepatic reduced/oxidized glutathione ratio and significantly lower hepatic SOD and glutathione peroxidase gene expression.

C-PC is effective in preventing atherosclerosis in adult hereditary hypercholesterolemic mice [37]. In vitro, C-phycocyanin also improved glucose production and expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) in high-glucose-induced insulin-resistant HepG2 cells [38]. C-alginin also increases glucose uptake in high glucose-induced insulin-resistant HepG2 cells through the insulin receptor substrate (IRS)/PI3K/Akt and Sirtuin-1 (SIRT1)/liver kinase B1 (LKB1)/AMPK signaling pathways, activates glycogen synthase, and increases the amount of glycogen [38]. C-phycocyanin can improve blood glucose and fasting serum insulin levels in tetracycline-induced diabetic mice [39]. Therefore, C-phycocyanin can maintain cellular glucose homeostasis by improving insulin resistance in hepatocytes.

6 Hepatoprotective role of C-phycocyanin in other liver diseases

Studies have shown that C-alginin can inhibit total serum cholesterol, triacylglycerol, LDL, ALT, AST, and malondialdehyde levels in mice modeled with alcoholic liver injury, significantly increase SOD levels in the liver, and promote the activation and proliferation of CD4+ T cells, which can have an ameliorative effect on alcoholic liver injury [40]. In addition, C-phycocyanin may enhance the intestinal barrier function, regulate the intestinal flora, reduce the translocation of bacteria and metabolites to the liver, and inhibit the activity of the Toll-like receptor 4 (TLR4)/NF-κB pathway, which may reduce the inflammation of the liver and prevent the occurrence of hepatic fibrosis in mice [41]. In mice with X-ray radiation-induced liver injury, C-phycocyanin can reduce radiation-induced DNA damage and oxidative stress injury by up-regulating the expression of nuclear factor (NF)-E2-related factor 2 (Nrf2) and downstream genes, such as HO-1, and play a hepatoprotective role by enhancing the activities of SOD and glutathione peroxidase [42].

7 Outlook

Liver fibrosis is the common final process of chronic liver diseases, and there is no effective therapeutic drug at present. Although some research progress has been made in the field of traditional Chinese medicine (TCM) on the reversal of liver fibrosis [43], its toxicological effects have not yet been clarified. Although the incidence of viral hepatitis has gradually decreased with the development and popularization of vaccines and antiviral drugs, the incidence of drug-induced liver injury (DILI) and liver diseases such as NAFLD has been increasing year by year with the improvement of people's living conditions [44]. Therefore, there is an urgent need to find drugs or nutrients that can help maintain normal hepatocyte function and effectively inhibit liver inflammation and fibrosis. C-alginin, with its anti-inflammatory, antioxidant, and antitumor effects, as well as good food coloring, has a wide range of applications in both the pharmaceutical and food industries.

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#phycocyanin #cphycocyanin #phycocyaninspirulina

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Reading And Interpreting Your Liver Function Test - A Guide To Commonly Used Liver Tests

The liver is a vital organ responsible for numerous metabolic functions in the body, including detoxification, protein synthesis, and bile production. Monitoring liver health is crucial for early detection and management of liver diseases. One of the primary tools for assessing liver function is the Liver Function Test (LFT). In this guide, we will delve into the commonly used liver tests, how to interpret the results, and what they indicate about your liver health.

Understanding Liver Function Tests

Liver Function Tests (LFTs) are a group of blood tests that provide valuable insights into the health and function of the liver. These tests measure various enzymes, proteins, and substances in the blood that are indicative of liver health.

Key components of Liver Function Tests

Alanine Aminotransferase (ALT): Elevated levels suggest liver damage, commonly caused by conditions like hepatitis or fatty liver disease.

Aspartate Aminotransferase (AST): Similar to ALT, elevated AST levels indicate liver damage but may also be elevated in conditions affecting the heart or muscles.

Alkaline Phosphatase (ALP): Elevated ALP levels may suggest liver or bone disease.

Total Bilirubin: Increased levels may indicate liver dysfunction or obstruction of bile ducts.

Albumin and Total Protein: These are measures of liver synthetic function; decreased levels may suggest liver disease.

What are the causes of abnormal liver function test results?

Causes of abnormal liver function test results can vary and may indicate different underlying conditions. Some common causes include:

1. Build-up of Fat in the Liver:

* Non-alcoholic fatty liver disease (NAFLD) can lead to abnormal liver function tests, especially in overweight or obese individuals.

2. Liver Inflammation and Damage:

* Infections, toxic substances like alcohol or certain medications, and immune conditions can cause liver inflammation and subsequent abnormal test results.

3. Liver Overworking:

* When the liver is under stress from processing medicines or toxic substances like alcohol or paracetamol, it can result in abnormal liver function tests.

4. Bile Duct Blockage:

* Blockages in the bile ducts, such as by gallstones, can lead to abnormal liver function test results.

5. Liver Conditions and Diseases:

* Underlying conditions like Wilson's disease, haemochromatosis, or Gilbert's syndrome can affect liver function and result in abnormal test values.

6. Liver Injury:

* Physical injury to the liver, trauma, or presence of abscesses or tumors within the liver can cause abnormal liver function tests.

7. Medications and Supplements:

* Certain medications, over-the-counter drugs, herbal remedies, and traditional medicines can also impact liver function test results.

8. Other Factors:

* Factors like high alcohol intake, viral infections, autoimmune conditions, metabolic liver diseases, heart problems, and tumors in the liver can contribute to abnormal liver function tests.

Continue Reading: https://www.healixhospitals.com/blogs/reading-and-interpreting-your-liver-function-test-a-guide-to-commonly-used-liver-tests

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Rheumatoid Arthritis:

Refer to rheumatologist.

●Nonpharmacologic measures – Nonpharmacologic measures, such as patient education, psychosocial interventions, and physical and occupational therapy, should be used in addition to drug therapy. Other medical interventions that are important in the comprehensive management of RA in all stages of disease include cardiovascular risk reduction and immunizations to decrease the risk of complications of drug therapies.

●Initiation of DMARD therapy soon after RA diagnosis – We suggest that all patients diagnosed with RA be started on disease-modifying antirheumatic drug (DMARD) therapy as soon as possible following diagnosis, rather than using antiinflammatory drugs alone, such as nonsteroidal antiinflammatory drugs (NSAIDs) and glucocorticoids (Grade 2C). Better outcomes are achieved by early compared with delayed intervention with DMARDs.

●Tight control of disease activity – Tight control treatment strategies to "treat to target" are associated with improved radiographic and functional outcomes compared with less aggressive approaches. Such strategies involve reassessment of disease activity on a regularly planned basis with the use of quantitative composite measures and adjustment of treatment regimens to quickly achieve and maintain control of disease activity if targeted treatment goals (remission or low disease activity) have not been achieved. (

●Pretreatment evaluation – Laboratory testing prior to therapy should include a complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), aminotransferases, blood urea nitrogen, and creatinine. Patients receiving hydroxychloroquine (HCQ) should have a baseline ophthalmologic examination, and most patients who will receive a biologic agent or Janus kinase (JAK) inhibitor should be tested for latent tuberculosis (TB) infection. Screening for hepatitis B and C should be performed in all patients. Some patients may require antiviral treatment prior to initiating DMARD or immunosuppressive therapy, depending upon their level of risk for hepatitis B virus (HBV) reactivation.

●Adjunctive use of antiinflammatory agents – We use antiinflammatory drugs, including NSAIDs and glucocorticoids, as bridging therapies to rapidly achieve control of inflammation until DMARDs are sufficiently effective. Some patients may benefit from longer-term therapy with low doses of glucocorticoids.

●Drug therapy for flares – RA has natural exacerbations (also known as flares) and reductions of continuing disease activity. The severity of the flare and background drug therapy influence the choice of therapies. Patients who require multiple treatment courses with glucocorticoids for recurrent disease flares and whose medication doses have been increased to the maximally tolerated or acceptable level should be treated as patients with sustained disease activity. Such patients require modifications of their baseline drug therapies.

●Monitoring – The monitoring that we perform on a regular basis includes testing that is specific to evaluation of the safety of the drugs being; periodic assessments of disease activity with composite measures; monitoring for extraarticular manifestations of RA, other disease complications, and joint injury; and functional assessment.

●Other factors affecting target and choice of therapy – Other factors in RA management that may influence the target or choice of therapy include the disabilities or functional limitations important to a given patient, progressive joint injury, comorbidities, and the presence of adverse prognostic factors.

Osteoarthritis

General principles – General principles of osteoarthritis (OA) management include providing continuous care that is tailored to the patient according to individual needs, goals, and values and should be patient-centered. Treatment can be optimized by OA and self-management education, establishing treatment goals, and periodic monitoring.

●Monitoring and assessment – The management of OA should include a holistic assessment which considers the global needs of the patient. Patient preferences for certain types of therapies should also be assessed, as compliance and outcomes can be compromised if the care plan does not meet the patient's preferences and beliefs.

●Overview of management – The goals of OA management are to minimize pain, optimize function, and beneficially modify the process of joint damage. The primary aim of clinicians should include targeting modifiable risk factors. Due to the modest effects of the individual treatment options, a combination of therapeutic approaches is commonly used in practice and should prioritize therapies that are safer.

●Nonpharmacologic therapy – Nonpharmacologic interventions are the mainstay of OA management and should be tried first, followed by or in concert with medications to relieve pain when necessary. Nonpharmacologic therapies including weight management and exercises, braces and foot orthoses for patients suitable to these interventions, education, and use of assistive devices when required.

●Pharmacologic therapy – The main medications used in the pharmacologic management of OA include oral and topical nonsteroidal antiinflammatory drugs (NSAIDs). Other options include topical capsaicin, duloxetine, and intraarticular glucocorticoids. Our general approach to pharmacotherapy is described below.

•In patients with one or a few joints affected, especially knee and/or hand OA, we initiate pharmacotherapy with topical NSAIDs due to their similar efficacy compared with oral NSAIDs and their better safety profile.

•We use oral NSAIDs in patients with inadequate symptom relief with topical NSAIDs, patients with symptomatic OA in multiple joints, and/or patients with hip OA. We use the lowest dose required to control the patient's symptoms on an as-needed basis.

•We use duloxetine for patients with OA in multiple joints and concomitant comorbidities that may contraindicate oral NSAIDs and for patients with knee OA who have not responded satisfactorily to other interventions.

•Topical capsaicin is an option when one or a few joints are involved and other interventions are ineffective or contraindicated; however, its use may be limited by common local side effects.

•We do not routinely use intraarticular glucocorticoid injections due to the short duration of its effects (ie, approximately four weeks).

•We avoid prescribing opioids due to their overall small effects on pain over placebo and potential side effects (eg, nausea, dizziness, drowsiness), especially for long-term use and in the older adult population.

•We do not routinely recommend nutritional supplements such as glucosamine, chondroitin, vitamin D, diacerein, avocado soybean unsaponifiables (ASU), and fish oil due to a lack of clear evidence demonstrating a clinically important benefit from these supplements. Other nutritional supplements of interest that may have small effects on symptoms include curcumin (active ingredient of turmeric) and/or Boswellia serrata, but the data are limited.

●Role of surgery – Surgical treatment is dominated by total joint replacement, which is highly effective in patients with advanced knee and hip OA when conservative therapies have failed to provide adequate pain relief.

●Factors affecting response to therapy – The discordance of radiographic findings to pain supports the notion that the mechanisms of pain are complex and likely multifactorial. The placebo effect is also known to impact response to therapy.

●Prognosis – Although there is great variability among individuals and among different phenotypes of OA, courses of pain and physical functioning have been found to be predominantly stable, without substantial improvement or deterioration of symptoms over time.

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Cholestasis during pregnancy

Cholestasis is a condition that affects the liver, gallbladder, and bile ducts. It can occur in two ways. Extrahepatic cholestasis occurs outside the liver (also known as non-obstetric cholestasis). Intrahepatic cholestasis, also called obstetric cholestasis, happens inside the liver. In pregnant women, hormones change the way bile flows through the gallbladder and the bile ducts. This causes bile to build up in the liver and spill into the bloodstream.

Obstetric cholestasis is a pregnancy-related liver disorder that occurs in approximately 1 in 200 women during their third trimester. It is marked by itching, high levels of serum aminotransferases and bile acids, and signs and symptoms that go away on their own two to three weeks after birth.

In severe obstetric cholestasis, the condition can be very serious and lead to premature birth, fetal distress, and stillbirth. Surgical treatment is usually recommended to prevent these complications and lessen the risk for you and your baby.

Fortunately, there is an effective treatment for obstetric cholestasis called ursodeoxycholic acid. It protects interstitial Cajal-like cells in the gallbladder from undergoing apoptosis by inhibiting TNF-a expression, thus preventing oxidative stress and thrombotic complications.

Cholestasis of pregnancy (also called intrahepatic cholestasis) is a liver disorder that can develop during your pregnancy. Your doctor will diagnose it by doing a physical exam and a blood test that shows how well your liver is functioning.

The tests will also measure how much bile acid is in your bloodstream. The more bile acids you have, the more likely you are to have cholestasis during pregnancy.

Intrahepatic cholestasis of pregnancy is a rare, reversible disease that typically occurs in the second half of pregnancy. It causes severe pruritus and an elevation of total serum bile acids, which may lead to jaundice in 10% of patients.

A pregnant woman with obstetric cholestasis (also called intrahepatic cholestasis of pregnancy) may experience itching without a rash. It typically starts in the third trimester and goes away after delivery.

Cholestasis occurs when bile, the digestive fluid that helps break down fats, does not leave the liver for the small intestine. This causes bile acids to build up in the bloodstream and cause itching.

The bile acids can also cause problems with a pregnant woman’s ability to absorb fat, and this can affect her blood clotting. This can also affect her baby, increasing the risk of stillbirth and premature birth.

Cholestasis occurs because of an impairment in the normal flow of bile. This leads to the accumulation of bile acids, bilirubin, and cholesterol.

The main cause of cholestasis is obstruction of the bile flow in the hepatocytes or cholangiocytes. This can happen for a number of different reasons.

One of the most common causes is a blockage in your gallbladder (bile ducts). Another cause is an obstruction in the liver or the tubes that carry bile from your stomach to your intestine.

You may need to take medication to help your bile move through your body more easily. This can reduce your itching and help your bile levels return to normal.

Cholestasis is a condition in which the flow of bile from your liver to your small intestine slows down or stops. This can happen due to problems with your liver, bile duct, or pancreas.

If you have obstetric cholestasis, your doctor will check for other health issues to help determine the cause. You'll have a physical exam and get blood tests to measure the level of bile acid in your blood as well as your liver function.

In most cases, obstetric cholestasis resolves after you deliver your baby. But you'll need to keep up with monitoring for a while after you give birth. You may have ultrasounds and fetal heart monitors to make sure your baby is okay.