In vitro and in silico biological studies of novel thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives

In the present study, we report the synthesis, characterization of new series of thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives 3a–f and 4a–f. The newly synthesized compounds were screened for in vitro antimicrobial and antiviral activities. The probable mode of action of these active compounds was determined through in silico docking study by docking the receptor methionyl-tRNA synthetase and human inosine-5′-monophosphate dehydrogenase (IMPDH) for antibacterial and antiviral activities, respectively. Among the compounds, 4c exhibited excellent in vitro antimicrobial activity against all tested strains with binding and docking energies ?35.6 and ?12.4 kcal/mol, respectively. The antiviral studies were carried out for the selected compounds in which 4a exhibited 73.69 and 54.42 % of inhibition of buffalopox and camelpox viruses, respectively. Furthermore, compound 4a showed minimum docking and binding energy along with the maximum hydrogen/hydrophobic interaction with IMPDH. The study contributes towards identification and screening of potential antimicrobial and antiviral agent’s against the pathogens.     

Antireticulin antibody in systemic sclerosis.

The prevalence, immunoglobulin class, and IgG subclass of antireticulin antibody in the serum samples of 32 patients with systemic sclerosis were investigated by indirect immunofluorescence on unfixed rodent tissue. Antireticulin antibody was present in 22/32 (69%) of patients and belonged to the IgG class in 19/22 (86%), the IgA class in 13/22 (59%), and the IgM class in 6/22 (27%) of positive sera. IgG1 was the predominant subclass of IgG antireticulin antibody, occurring either alone or in association with IgG3 in 12/19 cases (63%). Thus antireticulin antibody of the IgG and IgA classes is found in most patients with systemic sclerosis. The finding of an autoantibody with reactivity for collagen-like fibres in systemic sclerosis indicates that the antibody has a potential role in the pathogenesis of the disease, and as it belongs to the IgA class this suggests that it arises in response to antigens presented to the immune system at the mucosal level.     

Key associations for hepatitis C virus genotypes in the Middle East and North Africa

This study aimed to investigate the epidemiology of hepatitis C virus (HCV) genotypes in the Middle East and North Africa (MENA) through an analytical and quantitative meta-regression methodology. For the most common genotypes 1, 3, and 4, country/subregion explained more than 77% of the variation in the distribution of each genotype. Genotype 1 was common across MENA, and was more present in high-risk clinical populations than in the general population. Genotype 3 was much more present in Afghanistan, Iran, and Pakistan than the rest of countries, and was associated with transmission through injecting drug use. Genotype 4 was broadly disseminated in Egypt in all populations, with overall limited presence elsewhere. While genotype 2 was more present in high-risk clinical populations and people who inject drugs, most of the variation in its distribution remained unexplained. Genotypes 5, 6, and 7 had low or no presence in MENA, limiting the epidemiological inferences that could be drawn. To sum up, geography is the principal determinant of HCV genotype distribution. Genotype 1 is associated with transmission through high-risk clinical procedures, while genotype 3 is associated with injecting drug use. These findings demonstrate the power of such analytical approach, which if extended to other regions and globally, can yield relevant epidemiological inferences.     

Gastrointestinal parasites in rural dogs and cats in Selangor and Pahang states in Peninsular Malaysia

To estimate the current prevalence of gastrointestinal (GI) parasites in dogs and cats, a total of 105 fresh faecal samples were collected from rural areas in Peninsular Malaysia. Each faecal sample was examined for the presence of GI parasites by microscopic examination after formalin-ether concentration technique and for protozoa, trichrome and Ziehl-Neelsen staining were employed. The overall prevalence of GI parasitic infection was 88.6% (95% CI = 82.5–94.7) in which 88.3% of dogs and 89.3% of cats were infected with at least one parasites species, respectively. There were 14 different GI parasites species (nematodes, cestodes and protozoa) detected, including Ancylostoma spp. (62.9%), Toxocara spp. (32.4%), Trichuris vulpis (21.0%), Spirometra spp. (9.5%), Toxascaris leonina (5.7%), Dipylidium caninum (4.8%), Ascaris spp. (2.9%), Hymenolepis diminuta (1.0%) and others. General prevalence of GI parasites showed a significant difference between helminth (84.4%) and protozoa (34.3%) infections. Monoparasitism (38.1%) was less frequent than polyparasitism (46.7%). As several of these GI parasites are recognized as zoonotic agents, the results of this investigation revealed that local populations may be exposed to a broad spectrum of zoonotic agents by means of environmental contamination with dogs and cats faeces and this information should be used to mitigate public health risks. Prevention and control measures have to be taken in order to reduce the prevalence rates especially in socioeconomically disadvantaged communities where animals live in close proximity to people, poor levels of hygiene and overcrowding together with a lack in veterinary attention and zoonotic awareness.     

Vitamin B6 dose-dependently ameliorates renal hemodynamic toxicity of cisplatin in rat model of nephrotoxicity: the histopathologic and biochemical findings

Despite its significant anticancer activity, the clinical use of cisplatin is often limited by its undesirable side effects in the kidney known as nephrotoxicity. It is a common and often overlooked clinical entity that presents itself in the setting of oxidative stress-associated diseases in older individuals with renal failure. In this study, we investigated the antioxidant-protecting effects of vitamin B₆ in the kidney, with a view on the vasoregulatory role of renal pyridoxal 5′-phosphate at reducing the hemodynamic toxicity of cisplatin. Hence, 50 male Sprague–Dawley rats were randomly assigned in one of five groups of the study to receive a corresponding dose of either normal saline, vitamin B₆ (200 mg/kg/bw; i.m.) or cisplatin alone (7 mg/kg/bw; i.m.), or in combination with vitamin B₆ at low (100 mg/kg/bw; i.m.) and high dose (200 mg/kg/bw; i.m.) for 10 days as animal model of renal failure. Daily administration of cisplatin at a dose of 7 mg/kg/bw resulted in a significant increase in local and systemic oxidative stress of the kidney and a decrease in glomerular function as a result of early hemodynamic toxicity. Histopathological examinations of renal tissues revealed acute tubular necrosis with hyaline cast formation triggered by cisplatin over 9 days of the study, in addition to interstitial nephritis and tubular epithelial loss. Further biochemical studies in HVB group showed the protecting effects of supplemented vitamin B₆ at a high dose, including a slowdown in urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and ATPase activity up to 50 % when compared to the low-dose rats and controls. In high-dose animals, the normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that the antioxidant property of vitamin B₆ consistently increases with the dose intensity. The present study also provided evidence that high dose of vitamin B₆ prevented both functional and histological renal changes induced by cisplatin in rats, more efficient than low dose of the vitamin.