Natural Infection with Rabies Virus: A Histopathological and Immunohistochemical Study of Human Brains

OBJECTIVES: Despite all the efforts and increased knowledge of rabies, the exact mechanisms of infection and mortality from the rabies virus are not well understood. To understand the mechanisms underlying the pathogenicity of rabies virus infection, it is crucial to study the tissue that the rabies virus naturally infects in humans. METHODS: Cerebellum brain tissue from 9 human post mortem cases from Iran, who had been infected with rabies virus, were examined histopathologically and immunohistochemically to evaluate the innate immune responses against the rabies virus. RESULTS: Histopathological examination revealed inflammation of the infected cerebellum and immunohistochemical analyses showed an increased immunoreactivity of heat shock protein 70, interleukin-6, interleukin-1, tumor necrosis factor-alpha, caspase-3, caspase-9, toll-like receptor3 and toll-like receptor4 in the infected brain tissue. CONCLUSION: These results indicated the involvement of innate immunity in rabies infected human brain tissue, which may aggravate the progression of this deadly disease.

The Occurrence and Risk Assessment of Exposure to Aflatoxin M₁ in Ultra-High Temperature and Pasteurized Milk in Hamadan Province of Iran

OBJECTIVES: Aflatoxins are a category of poisonous compounds found in most plants, milk and dairy products. The present research was carried out to detect the presence of aflatoxin M₁ (AFM₁) in samples of milk collected from Hamadan province, Iran. METHODS: Twenty five samples of ultra-high temperature (UHT) and 63 samples of pasteurized milk were collected and the amount of AFM₁ was measured by an Enzyme-Linked Immunosorbent Assay method. In addition, the estimated daily intake (EDI) and hazard index (HI) of AFM₁ was determined by the following equations:(EDI= mean concentration of AFM₁ × daily consumption of milk/body weight; HI=EDI/Tolerance Daily Intake). RESULTS: AFM₁ was detected in 21 (84%) UHT milk samples and in 55 (87.30%) pasteurized milk samples. Seven (28%) samples of UHT and 21 (33.33%) pasteurized milk samples had higher AFM₁ content than the limit allowed in the European Union and Iranian National Standard Limits (0.05 μg/kg). None of the samples exceeded the US Food and Drug Administration limit (0.5 μg/kg) for AFM₁. EDI and HI for AM₁ through milk were 0.107 ng/kg body weight/day, and 0.535, respectively. CONCLUSION: A significant percentage of milk produced by different factories in Iran (84% of UHT and 87.3% of pasteurized milk) was contaminated with AFM₁. Therefore, more control and monitoring of livestock feeding in dairy companies may help reduce milk contamination with AFM₁. As the HI value was lower than 1, it can be assumed that there was no risk of developing liver cancer due to milk consumption.

Factors that Correlate with Poor Glycemic Control in Type 2 Diabetes Mellitus Patients with Complications

OBJECTIVES: Inadequate glycemic control amongst patients with Type 2 diabetes mellitus (T2DM) indicates a major public health problem and a significant risk factor for the progression and complications caused by diabetes. Glycemic control is the main therapeutic objective for the prevention of organ damage and other complications arising from diabetes. METHODS: This was a retrospective observational study of T2DM patients with complications, who were aged 40 years and older. The study was conducted retrospectively on medical records (in-patient and out-patient) obtained from a South Indian teaching hospital, Manipal, India. The patients included in the study had fasting blood sugar, postprandial blood sugar and HbA1c measured at least twice during follow-ups the previous year. Patients’ HbA1c levels were categorized into good control ≤7% (≤53mmol/mol), and poor control >7% (>53mmol/mol), and patients’ characteristics were analyzed. RESULTS: A total of 657 patients were included in the study. The mean age was 59.67 (SD = 9.617) years, with 152 (23.1%) females and 505 (76.9%) males, and 514 (78.2%) patients had poor glycemic control. Most of the patients were on insulin mono-therapy [n = 271 (42.1%)], about a third of the patients were on combination therapy that included an oral hypoglycemic agent and insulin [n = 236 (36.6%)]. Patients with a history of more than 10 years of diabetes [n = 293 (44.6%)], had a family history of diabetes [n = 256 (39%)] and obesity [n = 95 (14.5%)], all had poor glycemic control. CONCLUSION: This present study indicated a significant association of gender (female), age, high-density lipoprotein level, duration of diabetes and type of medication, with poor glycemic control in T2DM patients that had secondary medical complications.

Molecular characterisation of Klebsiella oxytoca strains isolated from patients with antibiotic-associated diarrhoea

Background and study aim: Colitis is a common complication after treatment with antibiotics such as beta-lactarns, quinolones, and aminoglycosides. Recently, Klebsiella oxytoca has been implicated in this type of diarrhoea. The prevalence and characterisations of K. oxytoca isolated from patients with antibiotic-associated diarrhoea were investigated. The K. oxytoca isolates were also tested for cytotoxin production

Patients and methods: This study was conducted from May 2011 to Dec 2013. Faecal samples were collected from hospitalised patients receiving antibiotic treatment. Initial cultivation was performed on specific media. The clinical isolates were confirmed by poIymerasc chain reaction [PCR] using the specific K. oxytoca po1ygalacturonase [pehX] gene. The double-disc diffusion test was used to detect extended-spectrum beta-lactamase [ESBL]-producing strains. Tracking of ESBL-encoding genes was performed via PCR. The organism was cultured on Hep-2 cell lines for cytotoxin production

Results: Out of 331 samples collected from patients, 40 were confirmed molecularly to be clinical isolates of K. oxytoca. Fourteen [35%] ESBL-producing strains were isolated using the double-disc diffusion method. Among the molecularly confirmed K. oxytoca isolated seven [17.5%] tested positive for the blaSHV gene, 12 [30%] for blaTEM, 10 [25%] for blaCTX-M, three [75%] for blaOXA, nine [22.5%] for blaCTX M-15, and seven [17.5%] for blaTEM-1. Five [12%] isolates showed cytotoxin activity below 30%, 12 [30%] strains showed moderate cytotoxin activity between 30% and 60%, and 23 [58%] strains showed cytotoxin activity >/=60%

Conclusions: the cytotoxin-producing K.oxytoca is found to be one of the causes of antibiotic-induced colitis. Discontinuing treatment and allowing normal intestinal flora to be established or prescribing appropriate medication after antibiogram can help patients with antibiotic-induced haemorrhagic colitis in a timely manner

α:Non-α and Gγ:Aγ globin chain ratios in thalassemia intermedia patients treated with hydroxyurea

<p><b>OBJECTIVES</b>To elucidate the possible ways by which hydroxyurea molecules affect globin chain (α or β-like) synthesis.</p><p><b>METHODS</b>A total of 23 thalassemia intermedia patients (13 male and 10 female) aged between 5 and 26 years were treated for five months with 15 mg/(kg·day) of hydroxyurea. Hemoglobins electrophoresis and globin chain electrophoresis was performed on each sample at different time points before and during the treatment.</p><p><b>RESULTS</b>Fetal hemoglobin increased significantly in most patients and average episodes of transfusion decreased. Both Gγ and Aγ-globin chains increased significantly and α-globin:Nonα-globin chain as well as Gγ-globin:Aγ globin chains ratios decreased.</p><p><b>CONCLUSIONS</b>Improvement in α:non-α ratio and consequent decrease of free α-globin chain might be the cause of beneficial effects of hydroxyurea therapy. Two patients who felt better didn't show significant increase in their fetal hemoglobin level, and this is in contradiction with the hypothesis claiming that the HbF level increase is the cause of such therapeutic effect. In spite of the unclear mechanism of action of this drug, hydroxyurea therapy had noticeable impacts on thalassemia intermedia and also sickle cell disease and even patients suffering from thalassemia major.</p>