Hypocholesterolemic effect of khellin and methoxsalen in male albino rats.

Khellin (CAS 82-02-0) and methoxsalen (CAS 298-81-7) were examined in male albino rats to evaluate their ability to modify serum lipoprotein cholesterol. Clinical chemistry parameters were also measured to obtain information indicative of possible drug toxicity. The drugs were evaluated in four-week double dose studies. After four weeks at 0.45 mg/100 mg b.wt. for khellin and 0.27 mg/100 g b.wt. for methoxsalen, per day, both drugs significantly lowered low density lipoprotein cholesterol, high density lipoprotein cholesterol and total cholesterol. Very low density lipoprotein cholesterol and triglycerides were not changed. No apparent toxicity was observed as clinical chemistry parameters and body weights were not different compared to control values. Similar results were observed with a lower dose of khellin (0.23 mg/100 g b.wt./d). A dose of 0.13 mg/100 g b.wt./d of methoxsalen had no observable effect in this study. Confirmation of the hypocholesterolemic activity of khellin and methoxsalen in this study enhances the therapeutic potential of these compounds against atherosclerosis.     

Calcineurin Inhibitor Withdrawal from Sirolimus-Based Therapy in Kidney Transplantation: A Systematic Review of Randomized Trials

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function, however, it also carries risk of acute rejection. We conducted a systematic review of randomized trials that involved CNI withdrawal from a sirolimus-based immunosuppressive regimen. The search strategy yielded six trials (n = 1047 patients) reported in eight publications. CNI withdrawal from sirolimus-based therapy, was associated with an increased risk of acute rejection (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87; 95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p = 0.76) were similar in both groups at 1 year. Hypertension was significantly reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p = 0.0006). CNI withdrawal from sirolimus-based therapy is associated with an increased risk of acute rejection in the short term with a significant improvement in renal function and a reduction in hypertension. Longer follow-up is needed to determine if these changes will result in a significant improvement in patient and graft survival.     

Measure of association between selenium status and sepsis in cattle

Odds ratio was used to evaluate relationship between sepsis in cattle less than 1 year old and mastitis in cows and erythrocyte glutathione peroxides (GSH-PX) activity as an indicator of selenium status. Data were from 178 blood samples collected from referred cases to Urmia University, Veterinary Teaching Hospital. Low activity of GSH-PX was significantly associated with higher odds of developing sepsis (P=0.005) in young cattle and mastitis (P=0.044) in adult cows. The odds ratios for the low activity of GSH-PX on incidence of sepsis and mastitis were 4.74 and 3.95, respectively. Selenium deficiency was associated with sepsis in young cattle and mastitis in cows, i.e., cattle with low activity of erythrocyte GSH-PX were at increased risk of sepsis and mastitis.     

Identification of Mycobacterium avium complex in sarcoidosis.

Cell wall-defective bacteria which later reverted to acid-fast bacilli have been isolated from sarcoid tissue. These have not been conclusively shown to be mycobacteria. Specific PCR assays were applied to identify mycobacterial nucleic acids in these cultured isolates and in fresh specimens obtained from patients with sarcoidosis. Positive amplification and hybridization were observed with Mycobacterium avium complex- and/or Mycobacterium paratuberculosis-specific probes in five of the six cultured isolates and two fresh skin biopsy samples and one cerebrospinal fluid specimen. There was no amplification or hybridization with Mycobacterium tuberculosis or M. avium subsp. silvaticum probes, respectively. Patients' sera were also tested for antibody reactivities by immunoblotting with M. paratuberculosis recombinant clones expressing the 36,000-molecular-weight antigen (36K antigen) (p36) and the 65K heat shock protein (PTB65K). All seven sarcoidosis, four of six tuberculosis, and all six leprosy patient serum specimens showed strong reactivity with p36 antigen. In contrast, 13 of 38 controls showed only weak reactivity with p36 (P = 0.002 for controls versus sarcoidosis samples). Similarly, PTB65K reacted with high intensity with sera from 5 of 5 sarcoidosis, 5 of 6 tuberculosis, and 5 of 6 leprosy patients, compared with its low-intensity reaction with 5 of 22 controls (P = 0.001 for controls versus sarcoidosis samples). This study demonstrates the isolation and/or identification of M. paratuberculosis or a closely related M. avium complex strain from sarcoid skin lesions and cerebrospinal fluid. Furthermore, the reactivity of antibodies in sarcoid patient sera against p36 and PTB65K antigens was comparable to the reactivity of sera obtained from patients with known mycobacterial disease. Collectively, these data provide further support for the theory of the mycobacterial etiology of sarcoidosis.     

Gut Hormones in Health and Obesity: The Upcoming Role of Short Chain Fatty Acids

We are currently facing an obesity pandemic, with worldwide obesity rates having tripled since 1975. Obesity is one of the main risk factors for the development of non-communicable diseases, which are now the leading cause of death worldwide. This calls for urgent action towards understanding the underlying mechanisms behind the development of obesity as well as developing more effective treatments and interventions. Appetite is carefully regulated in humans via the interaction between the central nervous system and peripheral hormones. This involves a delicate balance in external stimuli, circulating satiating and appetite stimulating hormones, and correct functioning of neuronal signals. Any changes in this equilibrium can lead to an imbalance in energy intake versus expenditure, which often leads to overeating, and potentially weight gain resulting in overweight or obesity. Several lines of research have shown imbalances in gut hormones are found in those who are overweight or obese, which may be contributing to their condition. Therefore, this review examines the evidence for targeting gut hormones in the treatment of obesity by discussing how their dysregulation influences food intake, the potential possibility of altering the circulating levels of these hormones for treating obesity, as well as the role of short chain fatty acids and protein as novel treatments.     

International spread of major clones of methicillin resistant staphylococcus aureus: nosocomial endemicity of multi locus sequence type 239 in Saudi Arabia and Romania

Phenotypically identified methicillin resistant Staphylococcus aureus (MRSA) strains from several hospitals in Romania and Saudi Arabia (n = 103 and 68, respectively) were confirmed to be MRSA by mecA PCR and PBP-2' based latex agglutination. Subsequently, strains were differentiated at the sub-species level using pulsed field gel electrophoresis (PFGE) of SmaI DNA macro-restriction fragments. Comparison of the PFGE fingerprints identified major clusters of strains, persistently present in the various hospitals. Endemicity of certain strains was identified, amongst others one due to a particularly methicillin resistant type in the burn wound sector of the Romanian hospital. No PFGE-based overlap was found between the Saudi and Romanian strains. However, multi locus sequence typing (MLST), performed for 20% of all strains, revealed that genuine genetic similarity was obscured by the PFGE analysis. In both the Romanian and Saudi hospitals the renowned sequence type (ST) 239 was very over-represented. This was especially apparent in Saudi Arabia, where all strains except two shared the ST 239 genotype. This clonal type has previously been identified in a variety of other countries. Despite the MLST concordance, PFGE data indicate that ST 239 diversifies while maintaining its core genome intact. ST 80, another previously but less frequently identified clone, was introduced in 2000 in the Romanian institutes and persisted over the past 3 years as a frequent cause of infections in a surgical department. The successful MRSA types can acquire prominent positions in hospitals of previously low-endemicity MRSA status.