A comprehensive design for prevention and management of COVID-19 in a tertiary medical institution in Bangladesh.

INTRODUCTION: Containment of the further spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reducing fatality due to coronavirus disease 19 (COVID-19) represent a pressing challenge to global health services. Here, we present a management blueprint for both the containment of SARS-CoV-2 and treatment of COVID-19 through a comprehensive approach. METHODOLOGY: A cohort of 130 consecutive patients identified as positive for SARS-CoV-2 by testing of nasal swab by polymerase chain reaction were managed at a peripheral city of Bangladesh between 1 April and 31 May, 2020. Based on their clinical status, 64 of them were initially selected for isolation (Isolation Group) and 66 recommended for hospitalization (Hospital Group) as per the direction of the "Central COVID-19 Control" Center. Both groups of patients were allocated to receive standard of care management and oxygen inhalation, and intensive care unit management as and when necessary. Based on the conditions of the COVID-19 patients, there was an active system of patients being transferred from the "Isolation Group" to "Hospital Group" and vice versa. RESULTS: Twelve patients of the "Isolation Group" were transferred to the hospital, as they exhibited symptoms of deterioration. Four patients of the "Hospital Group" died during the observation period of two months in the intensive care unit. However, there has been no fatality among the patients of the "Isolation Group". CONCLUSIONS: The concept of "Isolation" and "Hospital Management" with the participation of the community seems to be an effective management strategy for COVID-19 in developing countries.

Role of nitric oxide on zymosan-induced inhibition of crop emptying in chicks.

Zymosan, a component of yeast cell walls, reduces feed passage through the digestive tract in chicks (Gallus gallus), although the mechanism mediating this effect is poorly understood. Nitric oxide (NO) is associated with a variety of biological actions including effects on the immune system. In addition, it has been suggested that NO is involved in relaxation of the digestive tract and affects feed passage in mammals. It is therefore possible that NO might be related to zymosan-induced reduction of feed passage in chicks. However, the role of NO on the effect of zymosan feed passage has not been clarified yet. Thus, the purpose of the present study was to investigate whether NO is associated with zymosan-induced alteration of feed passage in chicks. Intraperitoneal (IP) injection of zymosan significantly increased plasma nitrate and nitrite (NOx) concentrations at 6 h after injection. Zymosan-induced elevation of plasma NOx concentration was abolished by co-injection of S-methylisothiourea (SMT), a selective inhibitor for inducible NO synthase (iNOS), indicating that zymosan facilitated the induction of iNOS. Furthermore, because zymosan increased iNOS mRNA expression in the digestive tract, NO is likely associated with the effect of zymosan on the digestive tract. IP injection of NO donors significantly decreased crop emptying rate, suggesting that NO functions as an inhibitor of crop emptying. This result implied that zymosan stimulates NO production by the induction of iNOS in the digestive tract and thereby inhibits crop emptying rate. However, the co-injection of SMT did not attenuate the inhibitory effect of zymosan on crop emptying. The present study provides evidence that some changes in the digestive tract caused by zymosan are mediated by iNOS-induced NO in chicks, but NO does not mediate the effect of zymosan on feed passage through the crop.

The expression of prosaposin and its receptors, GRP37 and GPR37L1, are increased in the developing dorsal root ganglion.

Prosaposin (PSAP), a highly conserved glycoprotein, is a precursor of saposins A-D. Accumulating evidence suggests that PSAP is a neurotrophic factor, as well as a regulator of lysosomal enzymes. Recently, the orphan G-protein-coupled receptors GPR37 and GPR37L1 were recognized as PSAP receptors, but their functions have not yet been clarified. In this study, we examined the distribution of PSAP and its receptors in the dorsal root ganglion (DRG) during development using specific antibodies, and showed that PSAP accumulates primarily in lysosomes and is dispersed throughout the cytoplasm of satellite cells. Later, PSAP colocalized with two receptors in satellite cells, and formed a characteristic ring shape approximately 8 weeks after birth, during a period of rapid DRG development. This ring shape, which was only observed around larger neurons, is evidence that several satellite cells are synchronously activated. We found that sortilin, a transporter of a wide variety of intracellular proteins containing PSAP, is strongly localized to the inner side of satellite cells, which contact the neuronal surface. These findings suggest that PSAP and GPR37/GPR37L1 play a role in activating both satellite and nerve cells.

Role of tenofovir and telbivudine in treatment of hepatitis B related acute on chronic liver failure.

INTRODUCTION: ACLF is characterized by acute deterioration of liver function in patients with chronic liver disease. HBV is one of the most important causes of both acute insult and underlying chronic liver disease in ACLF. Reactivation of HBV is one of the common causes of ACLF in our region. ACLF requires multiple organ support and is associated with high short and medium term mortality. This is the reason why early, rapid reduction of HBV DNA is essential in treating ACLF-B. METHODS: Consecutive patients of ACLF-B due to spontaneous reactivation of HBV (ALT> 5xULN or >2 x baseline and HBV DNA >20,000 IU/ml) were randomized into tenofovir group (300mg/day) and telbivudine group (600mg/day) along with standard medical treatment. Clinical and laboratory parameters were evaluated at baseline, day-7, day-14, day-30 and day-90. HBV DNA was evaluated at baseline and after three months of therapy. Primary end point was survival or death at three months. Secondary end point was improvement of liver function assessed by Child-Turcotte Pugh score and MELD score at three months. RESULTS: 30 patients were enrolled in the study and 15 of them received tenofovir and 15 patients received telbivudine. Most of the baseline parameters showed no difference except serum AST and serum creatinine level that showed statistically significant difference between two groups. After antiviral therapy both groups showed significant clinical improvement along with CTP and MELD scores. However statistically significant improvement between tenofovir and telbivudine groups was only seen with MELD score. Survival rate was 80% in tenofovir group and 60% in telbivudine group, but this was not statistically significant. Low serum albumin at baseline was predictor of mortality. CONCLUSION: In patients of ACLF-B, antiviral therapy with both tenofovir and telbivudine improve liver function, but there is no statistically significant difference in survival between tenofovir and telbivudine.

Implications of Birth-Dose Vaccination against Hepatitis B Virus in Southeast Asia.

The World Health Organization (WHO) South-East Asia Regional Office (SEARO) covers 11 countries with a combined population of about 2 billion people, making it the most populous of the six WHO regions. In 1992, the WHO advocated including the hepatitis B vaccine in the Expanded Program of Immunization (EPI) and vaccinating all infants and children three times within 1 year of birth (HepB3). Recently, the WHO advocate birth-dose hepatitis B vaccination (HepB-BD) as soon as possible after birth, preferably within 24 hours. In 2016, the SEARO endorsed a regional hepatitis B control goal with a target of hepatitis B surface antigen (HBsAg) seroprevalence of ≤1% among children aged ≥5 years by 2020. Of the 11 SEARO countries, four achieved this target on schedule. Out of these four countries, two countries (Bangladesh and Nepal) have not adopted HepB-BD in EPI program. On the other hand, the coverage of HepB3 is not satisfactory in some SEARO countries, including India which adopted HepB-BD but could not achieve the overall target of SEARO. Thus, it is a point of debate whether emphasis should be placed on proper implementation of HepB3 or whether a new agenda of HepB-BD should be incorporated in developing countries of SEARO. The article discusses strengthening and expanding the Hepatitis B vaccination program in SEARO countries with an emphasis on HepB and HepB-BD programs.

Behavioral and physiological responses to peripheral injection of flagellin in chicks.

Flagellin (Flg) is a globular protein, found in bacterial flagella, that serves as a pathogen-associated molecular pattern and also serves as a toll-like receptor-5 (TLR5) ligand in vertebrates. Most ligands for TLRs are involved in non-specific effects such as anorexia and hypoactivity in an animal infected by bacteria. However, there is little knowledge on the effects of Flg in birds. Therefore, the purpose of the present study was to determine if intraperitoneal (IP) injection of Flg affects food intake, voluntary activity, cloacal temperature, crop emptying rate, blood constituents, and splenic gene expression of cytokines in chicks (Gallus gallus). The effect of Flg22, an N-terminus fragment of Flg, was also investigated. IP injection of 10 µg Flg significantly increased the splenic gene expression of interleukin-8, interferon-γ (IFN-γ), and tumor necrosis factor-like cytokine-1A, suggesting that Flg activated the innate immune system in chicks. The injection of Flg significantly decreased food intake, voluntary activity, blood glucose concentration, and crop emptying rate, and increased cloacal temperature and plasma concentrations of nitrite, nitrate, and corticosterone. However, the injection of Flg22 only affected the splenic gene expression of IFN-γ, indicating that the full-length of Flg is required for its action. These results suggest that Flg, a ligand for TLR5, is related to non-specific symptoms including anorexia, hypoactivity, increase in body temperature, disturbance of food passage in the digestive tract, and the activation of hypothalamic-pituitary-adrenal axis during bacterial infection in chicks.

Reply to "Ivermectin Treatment May Improve the Prognosis of Patients With COVID-19" / Respuesta a "El tratamiento con ivermectina puede mejorar el pronóstico de los pacientes con COVID-19"

No disponible

Prosaposin and its receptors GRP37 and GPR37L1 show increased immunoreactivity in the facial nucleus following facial nerve transection.

Neurotrophic factor prosaposin (PS) is a precursor for saposins A, B, C, and D, which are activators for specific sphingolipid hydrolases in lysosomes. Both saposins and PS are widely contained in various tissues. The brain, skeletal muscle, and heart cells predominantly contain unprocessed PS rather than saposins. PS and PS-derived peptides stimulate neuritogenesis and increase choline acetyltransferase activity in neuroblastoma cells and prevent programmed cell death in neurons. We previously detected increases in PS immunoactivity and its mRNA in the rat facial nucleus following facial nerve transection. PS mRNA expression increased not only in facial motoneurons, but also in microglia during facial nerve regeneration. In the present study, we examined the changes in immunoreactivity of the PS receptors GPR37 and GPR37L1 in the rat facial nucleus following facial nerve transection. Following facial nerve transection, many small Iba1- and glial fibrillary acidic protein (GFAP)-positive cells with strong GPR37L1 immunoreactivity, including microglia and astrocytes, were observed predominately on the operated side. These results indicate that GPR37 mainly works in neurons, whereas GPR37L1 is predominant in microglia or astrocytes, and suggest that increased PS in damaged neurons stimulates microglia or astrocytes via PS receptor GPR37L1 to produce neurotrophic factors for neuronal recovery.

Increased Proinflammatory Cytokine Production by Chronic Hepatitis B Patients with Mutant Hepatitis B Virus: Plausible Mechanisms Underlying Severe Liver Diseases in These Patients.

Hepatitis B virus (HBV) is a noncytopathic virus and billions of HBV-infected patients live uneventful lives and do not suffer from notable liver damage. However, HBV also causes progressive liver diseases characterized by hepatic inflammation, hepatic fibrosis, and liver cancer in millions of HBV-infected patients. The goal of this study was to evaluate the role of mutant HBV in HBV pathogenesis. In a cohort of 360 chronic HBV-infected patients, mutations at T1762/A1764 of HBV genome were detected in most of the patients with HBV-induced liver cirrhosis and hepatocellular carcinoma. To explore if mutations at T1762/A1764 of HBV genome has any role in progressive liver disease, peripheral blood mononuclear cells (PBMCs) and antigen-presenting dendritic cells (DCs) were isolated from five chronic hepatitis B (CHB) patients with mutations at T1762/A1764 and five comparable patients of CHB without mutations at T1762/A1764. DCs were pulsed with hepatitis B surface antigen (HBsAg). The levels of cytokines produced by PBMCs and DCs as well as nitrite production by DCs were evaluated. Significantly higher levels of interleukin-12, tumor necrosis factor-alpha, interferon-gamma, and transforming growth factor-beta were detected in cultures of PBMCs, DCs, and HBsAg-pulsed DCs from CHB patients with mutations at T1762/A1764 compared with those without mutations (p < 0.05). DCs of all CHB patients with mutations produced significantly higher levels of nitrite compared with those without mutation at T1762/A1764 (p < 0.001). This study discusses the inflammatory potential of mutant HBV that may be responsible for diverse levels of pathogenicity of HBV. Further studies involving larger cohorts would provide more insight into these unresolved issues about HBV pathogenesis and these insights may aid in developing immune therapy for CHB patients.

Age- and sex-associated changes in prosaposin and its receptors in the lacrimal glands of rats.

Prosaposin, a saposin precursor, is a potent neurotrophic factor found in several tissues and various biological fluids. Saposin-deficient patients have different ophthalmic disorders, indicating a relationship between ocular health and prosaposin. However, there is little information about prosaposin on the ocular surface. Because ocular functions are diverse and depend on age and sex, we examined whether prosaposin and its receptors, G protein-coupled receptor 37 (GPR37) and GPR37L1, are expressed in the major ocular glands, the extra orbital lacrimal gland (ELG), and harderian gland (HG) of rats and whether sex and aging affect their expression. Immunohistochemical analyses revealed that prosaposin and its receptors were expressed in the ELGs and HGs of rats, although their expression varied based on the type of gland, age, and sex. Prosaposin, GPR37, and GPR37L1 were expressed in the basolateral membranes and cytoplasm of acinar cells of the ELGs, and their immunoreactivities were higher in female rats of menopausal age than age-matched male rats. However, such age- and sex-related differences in the immunoreactivities of prosaposin, GPR37, and GPR37L1 were not observed in the HGs. Triple immunofluorescence labelling revealed that prosaposin, GPR37, and GPR37L1 were co-localised in the acinar and ductal cells in the ELGs, although the degrees of colocalization varied according to the age and sex of the rats. Together, the present results showed that prosaposin and its receptors were expressed in the major ocular glands of rats, and their immunoreactivities to the ELGs differed considerably with age and sex.

Physiological responses to central and peripheral injections of compound 48/80 and histamine in chicks.

Mast cells are a type of immune cell widely distributed in the body of vertebrates. Mast cells have many granules that contain several bioactive molecules such as histamine, and these molecules are released through degranulation when the mast cell receives certain stimuli. Because the number of mast cells increases during infection in chickens (Gallus gallus), the activity of mast cells might be related to non-specific symptoms such as anorexia under an infectious condition. Therefore, the purpose of the present study was to investigate whether intraperitoneal (IP) and intracerebroventricular (ICV) injections of compound 48/80, which induces degranulation of mast cells, affects feeding, voluntary activity, cloacal temperature, and the concentrations of plasma corticosterone (CORT) and glucose in chicks. The effect of histamine, which is found in mast cell granules, on these parameters was also investigated. IP injection of compound 48/80 significantly decreased food intake, voluntary activity, and cloacal temperature, and increased plasma CORT concentration in the chicks. While ICV injection of compound 48/80 also decreased food intake, it increased cloacal temperature and plasma glucose concentration. Both IP and ICV injections of histamine significantly decreased food intake, cloacal temperature, and plasma CORT concentration. However, only IP injection of histamine significantly decreased voluntary activity and increased plasma glucose concentration. The results suggest that degranulation of mast cells is related to non-specific symptoms in chicks, although the mechanism seems to be different between peripheral and central tissues. In addition, the effect of peripherally-injected compound 48/80 may be partly mediated by histamine.

Compound 48/80 reduces the crop-emptying rate, likely through a histamine-associated pathway in chicks.

Infectious conditions are associated with reduced food passage through the digestive tract in both mammals and chicks; however, the precise mechanism mediating this response in chicks remains unclear. The purpose of the present study was to determine if mast cells, a blood cell type which plays an important role in the immune system, might affect food passage through the digestive tract in chicks. Specifically, we performed intraperitoneal (IP) injections of compound 48/80, an inducer of mast cell degranulation, and measured crop emptying. The IP injection of compound 48/80 significantly reduced the crop-emptying rate, but it did not affect the proventriculus to small intestine transit rate or the number of defecations. We also found that IP-injected histamine, which is secreted by mast cells, also reduced the crop-emptying rate. In addition, IP injection of 2-pyridylethylamine (histamine H1 receptor agonist), but not dimaprit, (R)-(-)-α-methylhistamine, and VUF8430 (histamine H2, H3, and H4 receptor agonists, respectively), reduced the crop-emptying rate, implying that histamine reduces the crop emptying rate via the histamine H1 receptor. Finally, we found that IP injection of compound 48/80 reduced mRNA expression of histidine decarboxylase, a rate-limiting enzyme for histamine synthesis, in the esophagus and proventriculus at 1 h and the proventriculus and duodenum at 3 h after the injection. In sum, the present study suggests that the degranulation of mast cells causes a reduction in the crop-emptying rate, possibly via the histamine pathway in chicks.

Treatment by Transarterial Chemoembolization and Sorafenib for Hepatocellular Carcinoma vs Advanced Hepatocellular Carcinoma in Bangladesh: A Real-life Situation.

BACKGROUND: Although there are thousands of patients with hepatocellular carcinoma (HCC) in Bangladesh, almost there is no nationwide recommendations for therapeutic maneuver for HCC patients. As most of the HCC patients of Bangladesh are diagnosed late, patients with advanced HCC with large and multiple HCC nodules represent the usual presentation of HCC. The study is presented here to assess the effects of a combined therapy of transarterial chemoembolization (TACE) and sorafenib in advanced HCC patients. MATERIALS AND METHODS: A total of 77 patients with advanced HCC were enrolled in this study. All of them had advanced HCC with variable etiologies and clinical conditions. All patients were treated by TACE and also given systemic sorafenib at the same time. The patients were checked 1 and 3 months after therapy commencement. RESULTS: Out of 77 patients, 18 patients died within 1 month and additional 15 patients died within 3 months after therapy commencement. Thus, there remains 44 surviving patients after 3 months. When different parameters of dead patients and survived patients were compared, no specific parameters dictated the factors about overall survival of more than 3 months. DISCUSSION: This is the first approach to initiate an invasive and a systemic therapy for treatment of advanced HCC in Bangladesh. Further follow-up of patients and their long-term overall survival may cast some lights about the role of these therapies in Bangladeshi HCC patients. HOW TO CITE THIS ARTICLE: Al Mahtab, M, Rahim MA, Noor-E-Alam SM, et al. Treatment by Transarterial Chemoembolization and Sorafenib for Hepatocellular Carcinoma vs Advanced Hepatocellular Carcinoma in Bangladesh: A Real-life Situation. Euroasian J Hepato-Gastroenterol 2019;9(2):63-66.

High Prevalence of Wilson's Diseases with Low Prevalence of Kayser-Fleischer Rings among Patients with Cryptogenic Chronic Liver Diseases in Bangladesh.

BACKGROUND: Chronic liver disease (CLD) is common in Bangladesh; however, a major bulk remains as cryptogenic CLD as they remain devoid of known pathological agents leading to have a check of Kayser-Fleischer (K-F) rings for possible Wilson's disease (WD) and many of these patients develop complications such as cirrhosis of liver and hepatocellular carcinoma. However, there remains considerable proportions of CLD patients with undefined etiology (cryptogenic CLD) and these patients cannot be provided effective therapy based on etiological factors. Here, the proportion of WD among cryptogenic CLD patients in Bangladesh has been evaluated to improve the management of CLD and reduce complications. MATERIALS AND METHODS: A total of 941 patients with cryptogenic CLD [negative for hepatitis viruses, alcohol, nonalcoholic fatty liver disease (NAFLD), drug, and autoimmunity] were enrolled in the study. To assess if they have been suffering from WD, the levels of copper in 24-hour urine were evaluated. Definitive WD was diagnosed when 24-hour urinary copper output was >100 µg and strongly indicative WD patients excreted >40 µg of copper in 24 hours. RESULTS: Out of 941 patients with cryptogenic CLD, 212 patients were diagnosed as definitive WD and 239 patients as strongly indicative WD on the basis of 24-hours copper excretion. The age distribution ranging of the patients varied from 1 year to 90 years. There was a male predominance. Considerable numbers of WD patients had previous history of jaundice. Kayser-Fleischer rings were mostly uncommon and detected in five patients with WD only. DISCUSSION: Wilson's disease is not a rare entity in Bangladesh; rather, it seems to be fairly common among CLD patients. A country-wide epidemiological survey should be conducted for diagnosis of WD in Bangladesh to provide a proper management strategy for these huge numbers of WD patients. In fact, most of the WD patients are unaware of their diagnosis and the general physicians are equally unaware of diagnosis and management of WD. HOW TO CITE THIS ARTICLE: Choudhury N, Quraishi SB, Atiqullah AKM, et al. High Prevalence of Wilson's Diseases with Low Prevalence of Kayser-Fleischer Rings among Patients with Cryptogenic Chronic Liver Diseases in Bangladesh. Euroasian J Hepato-Gastroenterol 2019;9(2):67-70.

Physiological response to central and peripheral injection of prostaglandin D2 in chicks.

Prostaglandin D2 (PGD2) is associated with a diverse array of functions in mammals including regulation of appetite, body temperature, sleep, and immune responses. Although much is known about the effects of PGD2 in mammals, there is a lack of information about its effects in birds. Therefore, the purpose of the present study was to determine if intracerebroventricular (ICV) and intraperitoneal (IP) injections of PGD2 affect feeding, voluntary movement, crop-emptying rate, corticosterone release, and cloacal temperature in chicks (Gallus gallus). ICV injection of PGD2 was associated with a reduction in food intake, a reduction in voluntary movement, an increase in the time spent sitting, a decline in crop emptying rate, and also short-term hypothermia. Central injection of PGD2 also decreased the plasma glucose concentration in chicks while it tended to increase the plasma corticosterone concentration. On the other hand, except for crop emptying, such physiological changes are not observed after IP injection of PGD2. In sum, the present study suggests that PGD2 induces anorexia, change in behavior, decline in crop empting rate, hypoglycemia and hypothermia, but most of these effects are exerted via central nervous system in chicks.