Comparative impact of streptozotocin on altering normal glucose homeostasis in diabetic rats compared to normoglycemic rats.

Diabetes mellitus is a syndrome and an endocrine disorder, primarily considered as a loss of glucose homeostasis because of the insulin action and/or secretion or both. Currently there are more than 150 million people in the world affected by diabetes mellitus with a higher share of Asian and European countries. The current study aimed to investigate the comparative altering properties of streptozotocin (STZ), based on up-turn and down-turn configuration of biochemical, toxicological and hematological parameters in comparison with normoglycemic male albino rats. This comparative study was conducted among normoglycemic and STZ based induced-type 2 diabetic male albino rats groups. The male albino rats were intra-peritoneally injected with STZ with the dose rate of 65 mg/kg body weight for one time to developed type 2 diabetic model. Biochemical (blood glucose, uric acid, urea and creatinine), toxicological (AST, ALT and ALP) and hematological parameters (red and white blood cells) and their functional indices were evaluated in type 2 diabetic induced group along with normoglycemic rats. The STZ based induced- type 2 diabetic rats showed statistically significance (p < 0.001) higher level in the blood glucose, alongwith the change in the levels of biochemical parameters including urea, uric acid, and creatinine. Toxicological parameters comprising AST, ALT and ALP were also shown significance (p < 0.001) as sufficient after experimental evaluation of biologically important parameter in STZ based induced-type 2 diabetic rats. Likewise, the red blood cells, white blood cells and their efficient components were exposed significantly insufficient after the injecting of STZ to induce the rats as type 2 diabetic. The results of the current study indicates the comparatively higher levels of variation among biochemical, toxicological and hematological parameters in STZ based Induced-type 2 diabetic model as compared to normoglycemic group.

Prescribing Patterns for Upper Respiratory Tract Infections: A Prescription-Review of Primary Care Practice in Quetta, Pakistan and the Implications.

Background: To identify and address the potential overuse of antibiotics, it is important to ascertain the prescribing practices of physicians. We, therefore, conducted this prescription analysis to document URTI-specific antibiotic prescription frequency in a public primary healthcare setting of Quetta city, Pakistan. Methods: A retrospective record review was conducted of all prescriptions for URTIs in Combined Military Hospital, Quetta from 1 March to 31st May 2021. The Mann-Whitney U and Jonckheere-Terpstra test was used to evaluate the association between the tendencies of a different group of prescribers. p-value of <0.05 was of statistical significance. Results: Over the 3 months, 50,705 prescriptions were screened and analyzed according to the established inclusion and exclusion criteria. A total of 4,126 (8.13%) URTI prescriptions met the inclusion criteria, of which 2,880 (69.80%) prescriptions contained antibiotics. Among all antibiotics, penicillins (Amoxicillin + Clavulanate) were the most prescribed antibiotic, constituting 1,323 (45.9%) of total antibiotics prescribed for all cases, followed by the Macrolide group 527 (18.2%). The Jonckheere-Terpstra test revealed a statistically significant association between the status of the prescriber and the diagnosis (p = 0.002). Furthermore, a moderate positive trend was reported with specialists being more competent in antibiotic prescribing based on their diagnosis, followed by postgraduates and house officers (τ = 0.322). Conclusion: The prescribing patterns for the management of URTIs in the hospital were inconsistent with current guidelines. Strict adherence to guidelines must be ensured and antibiotic prescribing for URTIs should be discouraged.

Diabetes-related Knowledge, Medication Adherence, and Health-related Quality of Life: A Correlation Analysis.

CONTEXT: Even though positive treatment outcomes for type 2 diabetes mellitus (T2DM) are linked to disease knowledge and adherence to medications, inadequate knowledge, poor adherence, and resistance to lifestyle modifications are still common among patients. This situation has been a continuing dilemma for patients and healthcare providers, and these factors negatively affect the health-related quality of life (HRQoL) of patients. OBJECTIVE: The current study intended to evaluate the correlations between diabetes-related knowledge, medication adherence, and HRQoL among T2DM patients in Pakistan. DESIGN: The study was designed as a questionnaire-based, cross-sectional descriptive analysis, with participants being selected using a prevalence-based sampling method. SETTING: The study was conducted at four different healthcare institutes namely Sandeman Provincial Hospital, Bolan Medical Complex Hospital, Al-Khair Hospital and Sajid Hospital, Quetta city, Pakistan. PARTICIPANTS: Participants were 300 patients with T2DM who were receiving treatment at public and private healthcare institutes in Quetta, Pakistan. OUTCOME MEASURES: In addition to collection of demographics, the Urdu version of Michigan Diabetes Knowledge Test (MDKT-U), the Drug Attitude Inventory (DAI-10), and the EuroQol EQ-5D were used to assess diabetes-related knowledge, medication adherence and HRQoL, respectively. The relationships among the 3 variables were determined using the Spearmen rho correlation coefficient, and the results were interpreted using Cohen' criteria. SPSS v.20 was used for data analysis, and P < .05 was considered significant for all analysis. RESULTS: The mean diabetes-related knowledge score was 5.83 ± 1.92, indicating participants' lack of knowledge of T2DM. Moderate adherence was reported, with a mean adherence score of 4.94 ± 2.72. Additionally, the mean EQ-5D score was 0.48±0.36, and the mean Visual Analogue Score (VAS) was 54.58 ± 20.28, highlighting poor HRQoL. The Spearman's rho correlation coefficient indicated significant, moderate correlations among all variables (P < .05; r = 0.053-0.231). CONCLUSIONS: The study found limited diabetes-related knowledge, moderate medication adherence, and poor HRQoL among patients with T2DM in Pakistan. Nevertheless, a positive significant correlation revealed that a directly proportional change in one study variable can improve the others.

Serological and Molecular Investigation of Brucellosis in Breeding Equids in Pakistani Punjab.

Brucellosis is an important zoonosis worldwide. Equines are susceptible to the infection when in close contact with infected animals. The objective of our study was to update the existing knowledge and detect and differentiate the causative agent of brucellosis in breeding equines in Punjab, Pakistan. A cross-sectional study was designed to evaluate the occurrence and etiology of the infection in the equine population in three districts. A total of 448 equine sera were collected from three prefectures viz. Sahiwal, Khanewal, and Okara of the Punjab Province of Pakistan. Ninety-six (21.4%) samples were found positive by RBPT, 3.56% (16/448) by iELISA, and 4.24% (19/448) by CFT. Real-time PCR demonstrated the presence of Brucella abortus-DNA in sero-positive samples. Age and location were found as risk factors. The study concludes equine brucellosis seroprevalence in the country where Brucella abortus as the main etiology. Fistulous withers and poll evil cases should be treated with care as they could be hazardous and a source of zoonotic transmission. Routine screening at an early age, vaccination in ruminants, and consumption of pasteurized dairy milk in humans is recommended for prevention of the infection. Specific tests need to be standardized and validated.

Modification of intestinal microbiota and its consequences for innate immune response in the pathogenesis of campylobacteriosis.

Campylobacter jejuni is the leading cause of bacterial food-borne gastroenteritis in the world, and thus one of the most important public health concerns. The initial stage in its pathogenesis after ingestion is to overcome colonization resistance that is maintained by the human intestinal microbiota. But how it overcomes colonization resistance is unknown. Recently developed humanized gnotobiotic mouse models have provided deeper insights into this initial stage and host's immune response. These studies have found that a fat-rich diet modifies the composition of the conventional intestinal microbiota by increasing the Firmicutes and Proteobacteria loads while reducing the Actinobacteria and Bacteroidetes loads creating an imbalance that exposes the intestinal epithelial cells to adherence. Upon adherence, deoxycholic acid stimulates C. jejuni to synthesize Campylobacter invasion antigens, which invade the epithelial cells. In response, NF- κ B triggers the maturation of dendritic cells. Chemokines produced by the activated dendritic cells initiate the clearance of C. jejuni cells by inducing the actions of neutrophils, B-lymphocytes, and various subsets of T-cells. This immune response causes inflammation. This review focuses on the progress that has been made on understanding the relationship between intestinal microbiota shift, establishment of C. jejuni infection, and consequent immune response.

Discrimination of multilocus sequence typing-based Campylobacter jejuni subgroups by MALDI-TOF mass spectrometry.

BACKGROUND: Campylobacter jejuni, the most common bacterial pathogen causing gastroenteritis, shows a wide genetic diversity. Previously, we demonstrated by the combination of multi locus sequence typing (MLST)-based UPGMA-clustering and analysis of 16 genetic markers that twelve different C. jejuni subgroups can be distinguished. Among these are two prominent subgroups. The first subgroup contains the majority of hyperinvasive strains and is characterized by a dimeric form of the chemotaxis-receptor Tlp7(m+c). The second has an extended amino acid metabolism and is characterized by the presence of a periplasmic asparaginase (ansB) and gamma-glutamyl-transpeptidase (ggt). RESULTS: Phyloproteomic principal component analysis (PCA) hierarchical clustering of MALDI-TOF based intact cell mass spectrometry (ICMS) spectra was able to group particular C. jejuni subgroups of phylogenetic related isolates in distinct clusters. Especially the aforementioned Tlp7(m+c)(+) and ansB+/ ggt+ subgroups could be discriminated by PCA. Overlay of ICMS spectra of all isolates led to the identification of characteristic biomarker ions for these specific C. jejuni subgroups. Thus, mass peak shifts can be used to identify the C. jejuni subgroup with an extended amino acid metabolism. CONCLUSIONS: Although the PCA hierarchical clustering of ICMS-spectra groups the tested isolates into a different order as compared to MLST-based UPGMA-clustering, the isolates of the indicator-groups form predominantly coherent clusters. These clusters reflect phenotypic aspects better than phylogenetic clustering, indicating that the genes corresponding to the biomarker ions are phylogenetically coupled to the tested marker genes. Thus, PCA clustering could be an additional tool for analyzing the relatedness of bacterial isolates.

Prevalence of HCV among the young male blood donors of Quetta region of Balochistan, Pakistan.

BACKGROUND: Hepatitis C, caused by hepatitis C virus (HCV) is a contagious disease of the liver which infects more than 170 million people world-wide and around 16 million in Pakistan. HCV associated infection spreads mainly by blood-to-blood contact. In recent years, many studies have been conducted to determine the prevalence of HCV infection in Pakistan; however, no data is available on HCV infection from the largest province of Pakistan. Therefore, the present study focuses on the prevalence of HCV infection in the young male blood donor population of Quetta region of Balochistan, Pakistan. METHODS: A total of 356 blood samples were collected from blood donors (age range 17-25 years) at Combined Military Hospital (CMH), Quetta, Balochistan, Pakistan. Blood samples were screened for HCV positivity by Immunochromatographic test (ICT) and Enzyme Linked Immunosorbant Assay (ELISA). RESULTS: Out of 356 blood samples, the overall HCV prevalence was 20.8%. Among the HCV positive cases, the age group with 25 years was more frequently infected with a prevalence of 26.3%. CONCLUSIONS: The present study provides the preliminary information about high HCV prevalence among the young male donor population in Balochistan province. This data may be helpful in formulating public health strategy for the prevention of risk factors associated with spreading of the disease. Furthermore, we recommend that in public sector hospitals and health care units ELISA should be preferred for anti-HCV detection over ICT.

Epidemiological association of Campylobacter jejuni groups with pathogenicity-associated genetic markers.

BACKGROUND: Campylobacter jejuni, the most leading cause for bacterial gastroenteritis worldwide, shows a high genetic diversity among its isolates. Recently, we demonstrated the existence of six C. jejuni-groups by combining MLST with six genetic markers. These groups were further characterized by the detection of cj1321-cj1326, fucP, cj0178, cj0755/cfrA, ceuE, pldA, cstII, and cstIII in order (I.) to show further associations between these different genetic markers and MLST CCs. Moreover, different studies were able to associate several of these markers: a sialylated lipoologosaccharide (cstII/III(+)), the gamma-glytamyl-transpeptidase (ggt(+)), and the absence of a certain allele of the enterochelin-uptake-binding-protein (ceuE(11168)(-)) with severe campylobacteriosis, bloody diarrhea and unpleasant outcome. Additionally more than half of human Campylobacter-isolates were assigned to a non-livestock clade associated with the absence of cj1321-cj1326. These isolates were considered as mere colonizers.From the combination of marker genes, the ratio of human isolates in a specific group, and clinical data (II.) it should be demonstrated to which of the previous defined groups these Campylobacter-subpopulations, associated with higher virulence, correspond. RESULTS: Besides the marker gene pldA, all new estimated genetic markers show significant differences in their distribution among the various MLST-based groups. Especially the genes for cj1321-cj1326, fucP, cj0178, cj0755/cfrA are widely associated with each other and split the study population into two major and seven intermediate groups substantiating the previous group-definition, whereas cstII and cstIII indicate at least three groups following an independent distribution pattern. CONCLUSIONS: Based on these data a group of C. jejuni-isolates characterized by the presence of ansB, dmsA, ggt, and the absence of cj1365c, cj1585c, cj1321-cj1326, fucP, cj0178, cj0755/cfrA, and cstII/III was associated with a higher prevalence in human campylobacteriosis, bloody diarrhea as well as hospitalization and bears obviously a higher virulence for humans. In contrast to that better livestock-adapted groups characterized by the ability to utilize L-fucose and the presence of all of the five identified putative C. jejuni iron-uptake systems as well as cj1321-cj1326, cj1365c, cj1585c, and cstII and/or cstIII (sialylated lipoologosaccharide) is more prevalent in animal hosts and was secondary associated with less severe campylobacteriosis.

A missense mutation (p.G274R) in gene ASPA causes Canavan disease in a Pakistani family.

Canavan disease (OMIM 271900) is an autosomal recessive lethal neurodegenerative disorder characterized by spongy degeneration of the brain. A highly consanguineous Pakistani family with Canavan disease was enrolled on the basis of diagnosis. All the affected individuals have mental retardation, megalocephaly and degradation of motor skills, poor head control, partial vision loss, weakness of the muscles and raised urinary concentration of N-acetyl aspartic acid in the urine. Blood samples were collected from affected as well as normal siblings and processed for DNA purification. Linkage analysis was performed by typing three short tandem repeat markers D17S1583 (7.19 cM), D17S1828 (10.02 cM) and D17S919 (14.69 cM) for an already-reported gene/locus ASPA at chromosome 17p13.2 causing Canavan disease. During linkage analysis, all the affected individuals were homozygous for short tandem repeat markers while the normal siblings were heterozygous showing co-segregation of the disease. Gene ASPA (NM_000049) was undertaken to sequence for mutation analysis. As a result of sequence analysis, we found missense substitution 740A→G (p.G274R) in exon 6 of gene ASPA. To our knowledge, this is the first report about Canavan disease on a Pakistani family.

Pancytopenia in two national ethnic groups of Baluchistan.

BACKGROUND: Pancytopenia is a recognisable haematological problem with common categorises diagnosis but best possible diagnostic approach is still to be defined. OBJECTIVE: The aim of this study was to determine the frequent causes and clinical presentation of pancytopenia in relation to age and sex in different ethnic groups of two national (Pakistani and Afghan) living in Baluchistan province. METHODS: This is a cross sectional descriptive type of study was carried out on patients (n = 180) for two years (July 2009-June 2011). Cases were successively registered in 2 provincial government hospital and 2 private clinics in Quetta with diagnosis of pancytopenia. RESULTS: The most frequent causes of pancytopenia in both national ethnic groups were malaria (29.44%) fallowed by tuberculosis (17.22%), leukaemia (16.67%), aplastic anaemia (13.33%), hepatitis (12.22%), other diseases (7.22%) and iron deficiency anaemia (3.89%). Overall, 63.89% male subjects were observed pancytopenia as compared to 36.11% female patients. The results also showed that patients with age > 41 years were highly (50%) affected by pancytopenia followed by 21-40 years (30.66%) and < 20 years (19.44%). Moreover, leukaemia cases were observed significantly higher in Afghan subjects (> 41 years). The most common symptom of patients was (71.11%) fever followed by Pallor (42.22%), fatigue (38.33%), weight loss (26.11%) and dizziness (25.56%). Leukaemia and aplastic anaemia were found to be the most serious causes of pancytopenia in Afghan ethnic group. CONCLUSIONS: Malaria, tuberculosis, aplastic anaemia, and leukaemia were the leading causes of pancytopenia in Pakistani and Afghan ethnic groups. Severe pancytopenia has significant relation with the clinical conclusion and can be used as a prognostic marker.