Native pentameric C-reactive protein displays more potent pro-atherogenic activities in human aortic endothelial cells than modified C-reactive protein

Inflammation is pivotal in atherogenesis. Numerous prospective studies have shown that levels of high sensitive C-reactive protein (CRP) predict cardiovascular events. Recently, data suggests that CRP could be a mediator in atherothrombosis. Loss of pentameric symmetry in CRP has been shown to result in the formation of modified CRP (mCRP). The main aim of this study was to examine the biological effects of the native, pentameric form of CRP compared to a modified form in human aortic endothelial cells. Human pentameric native CRP (n-CRP) from two different sources (recombinant and serum) was purified and used. It was then subjected to EDTA chelation and urea treatment to prepare modified CRP (m-CRP). Purity of both n-CRP and m-CRP preparations was checked by gel electrophoresis. Both n-CRP and m-CRP were incubated with human aortic endothelial cells (HAEC) and biological activities was tested by assaying for interleukin-8 (IL-8), plasminogen activator inhibitor-1(PAI-1), cyclic GMP and prostaglandin F1-alpha. n-CRP significantly upregulated IL-8 at concentrations > or = 10 microg/mL while m-CRP upregulated IL-8 only at concentrations of 50 microg/mL (p < 0.05). PAI-1 levels were significantly increased to a greater extent with native compared to m-CRP (p < 0.05). While both decreased PGF1-alpha at concentrations of 50 microg/mL, the effect of native CRP was more pronounced and was evident at 10 microg/mL (p < 0.05). The most pronounced difference was observed with regard to inhibition of eNOS activity as assessed by cGMP which was observed at 10 microg/ml of native CRP but only at 50 microg/mL for m-CRP (native CRP versus mCRP: p < 0.001). Thus, native pentameric CRP compared to modified CRP exerts more potent atherogenic effects in human aortic endothelial cells.     

Prevalence and antimicrobial susceptibility pattern of methicillin resistant Staphylococcus aureus: a multicentre study

Purpose: Methicillin resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen. We report the prevalence and antibiotic susceptibility pattern of MRSA in major southern districts of Tamilnadu. Methods: A total of 7172 clinical specimens and 1725 carrier screening samples were collected from different centers and subjected to MRSA screening using conventional microbiological methods. Subsequently the antibiotic sensitivity test was performed for the confirmed MRSA isolates. Results: Out of 906 strains of S. aureus isolated from clinical and carrier samples, 250 (31.1%) and 39 (37.9%) were found to be methicillin resistant respectively. Almost all clinical MRSA strains (99.6%) were resistant to penicillin, 93.6% to ampicillin, and 63.2% towards gentamicin, co-trimoxazole, cephalexin, erythromycin, and cephotaxime. All MRSA strains (100%) of carrier screening samples had resistance to penicillin and about 71.8% and 35.9% were resistant to ampicillin and co-trimoxazole respectively. Multidrug resistance was observed among 63.6% of clinical and 23% of carrier MRSA isolates. However, all strains of clinical and carrier subjects were sensitive to vancomycin. Conclusion: The determination of prevalence and antibiotic sensitivity pattern of MRSA will help the treating clinicians for first line treatment in referral hospitals.     

Phenomapping for the Identification of Hypertensive Patients with the Myocardial Substrate for Heart Failure with Preserved Ejection Fraction

We sought to evaluate whether unbiased machine learning of dense phenotypic data (“phenomapping”) could identify distinct hypertension subgroups that are associated with the myocardial substrate (i.e., abnormal cardiac mechanics) for heart failure with preserved ejection fraction (HFpEF). In the HyperGEN study, a population- and family-based study of hypertension, we studied 1273 hypertensive patients utilizing clinical, laboratory, and conventional echocardiographic phenotyping of the study participants. We used machine learning analysis of 47 continuous phenotypic variables to identify mutually exclusive groups constituting a novel classification of hypertension. The phenomapping analysis classified study participants into 2 distinct groups that differed markedly in clinical characteristics, cardiac structure/function, and indices of cardiac mechanics (e.g., phenogroup #2 had a decreased absolute longitudinal strain [12.8?±?4.1 vs. 14.6 ± 3.5%] even after adjustment for traditional comorbidities [p?<?0.001]). The 2 hypertension phenogroups may represent distinct subtypes that may benefit from targeted therapies for the prevention of HFpEF.     

&ldquo;Diabegon&rdquo;, a safe and effective polyherbal therapy for type 2 diabetes mellitus

AIM: To investigate the antihyperglycemic, antihyperlipidemic and antioxidant functions of a polyherbal formulation, “Diabegon”, in human subjects with type 2 diabetes mellitus. METHODS: A total of 33 human subjects with type 2 diabetes mellitus were recruited for the study and all anthropological and biochemical parameters were recorded at the time of registration. The subjects were given hot water extract obtained from 10 gm of “Diabegon” powder, “Diabegon kwath”, on an empty stomach everyday in the morning under personal supervision for 6 mo. The therapeutic functions of the “Diabegon kwath” was assessed by monitoring the blood glucose levels at monthly intervals and glycosylated hemoglobin, lipid profile and biomarkers of oxidative stress, liver and kidney function markers at three monthly intervals in the study subjects. RESULTS: Daily administration of hot water extract of “Diabegon” regularly for 6 mo resulted in significant reductions of blood glucose and glycosylated hemoglobin levels. There was also a significant increase in high density lipoprotein cholesterol levels with concomitant decreases in total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein. A significant improvement in glycosuria and proteinuria was also observed. Also, the subjects exhibited a significant improvement in enzymatic and nonenzymatic biochemical markers of oxidative stress. The kidney and liver functions remained normal and in fact improved in many subjects. CONCLUSION: The study which is first of its kind, advocates “Diabegon kwath” as a safe and effective Ayurvedic therapy for the treatment of human type 2 diabetes mellitus and further placebo controlled trial may substantiate the therapeutic efficacy of the formulation.     

Wound healing potential of Cassia fistula on infected albino rat model

BACKGROUND: Infection is the major problem to treat the wound. Antibiotic resistance by the pathogenic microorganism renders drug ineffective and calls for improved designing and development of new drugs. New approach has been developed to isolate active components from botanicals. Our aim was to investigate the potential of Cassia fistula to treat the infected wound on albino rat model. MATERIAL AND METHODS: The alcohol extract of C. fistula leaves was analyzed for antibacterial effect against Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa ATCC 27853. Formulated ointment was topically applied on the infected wound. Wound reduction rate, histological analysis, biochemical analysis, and gelatin zymography were obtained to assess the healing pattern. RESULTS: C. fistula treated rats showed, better wound closure, improved tissue regeneration at the wound site, and supporting histopathological parameters pertaining to wound healing. Biochemical analysis and matrix metalloproteinases expression correlated well with the results thus confirming efficacy of C. fistula in the treatment of the infected wound. CONCLUSION: Along with the other activities such as antitumor, antioxidant, hypoglycemic, hepatoprotective, antibacterial, hypocholesterolaemic, and antidiabetic activity, the healing potential of C. fistula provides a scientific rationale for the traditional use of this plant in the management of infected dermal wound and can be further investigated as a substitute to treat infected wounds without using synthetic antibiotics.     

Gut-lymph hypothesis of systemic inflammatory response syndrome/multiple-organ dysfunction syndrome: validating studies in a porcine model

BACKGROUND: Trauma-hemorrhagic shock (T/HS) mesenteric lymph from rats has multiple biological properties and appears to cause organ injury via the activation of neutrophils and endothelial cells. As the next step in testing the potential clinical relevance of these rodent studies, we utilized a swine T/HS model to determine whether the intestinal lymph results observed in the rodent could be replicated in swine. A porcine model was chosen because the pig and human cardiovascular and gastrointestinal physiology are similar. METHODS: Male pigs were subjected to T/HS and a major intestinal lymph duct was cannulated. Hemorrhagic shock (mean arterial pressure, 40 mm Hg) was performed by withdrawing blood, for 3 hours or until the base deficit reached -5. Animals were then resuscitated in two stages to mimic the prehospital and hospital phases of resuscitation. Mesenteric lymph was collected hourly throughout the experiment and its biological activity was tested on neutrophils (respiratory burst) and endothelial cells (monolayer permeability and cytotoxicity). RESULTS: T/HS lymph but not trauma-sham shock lymph (T/SS) increased neutrophil activation as reflected by an augmented respiratory burst. Likewise T/HS lymph collected at all time points up to 5 hours postshock significantly increased endothelial cell permeability by twofold or greater (p < 0.05), whereas T/HS lymph produced during the first 2 hours postshock was cytotoxic for endothelial cells (viability 70%, p < 0.05 vs. preshock). In contrast, T/SS lymph had no effect on the endothelial cells. CONCLUSION: This large animal model validates rodent studies showing that the shock-injured gut releases biologically active factors into the mesenteric lymph and these factors activate neutrophils and injure endothelial cells.     

Illuminating the Center: Mechanisms Regulating Lumen Formation and Maintenance in Mammary Morphogenesis

The lumens present in ductal structures are required for transport of fluids and air. Studies in model organisms and cells in culture suggest that lumens can be generated by multiple mechanisms including apoptosis of centrally located cells, and re-modeling of epithelia. Several studies point to a role for apoptosis during lumen formation in the mammary ducts. However, a role for other mechanisms during lumen formation in the mammary ducts is largely unexplored. Understanding how lumens are formed and maintained free of cells is of clinical importance because filling of the luminal space is associated with cancer and inflammation. Thus, further investigation can lead to new diagnostic and therapeutic opportunities.     

Total joint arthroplasty in the treatment of advanced stages of thumb carpometacarpal joint osteoarthritis

PURPOSE: Osteoarthritis of the thumb basal joint is a very common and disabling condition that frequently affects middle-aged women. Many different surgical techniques have been proposed for extensive degenerative arthritis of the first carpometacarpal (CMC) joint. Joint replacement has been an effective treatment of this condition. The purpose of this article is to present the outcome of a total cemented trapeziometacarpal implant in the treatment of more advanced stages of this disease. METHODS: Total joint arthroplasty of the trapeziometacarpal joint was performed on 26 thumbs in 25 patients to treat advanced osteoarthritis (Eaton and Littler stages III and IV) between 1998 and 2003. Indications for surgery after failure of conservative treatment were severe pain, loss of pinch strength, and diminished thumb motion that limited activities of daily living. A trapeziometacarpal joint prosthesis was the implant used in this series. The average follow-up time was 59 months. RESULTS: At the final follow-up evaluation, thumb abduction averaged 60 degrees and thumb opposition to the base of the small finger was present. The average pinch strength was 5.5 kg (85% of nonaffected side). One patient had posttraumatic loosening, which was revised with satisfactory results. Radiographic studies at the final follow-up evaluations did not show signs of atraumatic implant loosening. One patient complained of minimal pain, and the remaining 24 patients were pain free. CONCLUSIONS: In our series, total joint arthroplasty of the thumb CMC joint has proven to be efficacious with improved motion, strength, and pain relief. We currently recommend this technique for the treatment of stage III and early stage IV osteoarthritis of the CMC joint in older patients with low activity demands. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.     

Single- or double-blind treatment With Balsamodendron mukul and nifedipine in hypertensive patients

This study assessed and compared the effects of Balsamodendron mukul (an extract of the gum of a small tree) and nifedipine (a calcium-channel-blocking reference drug) on blood pressure, lipids, lipoproteins, and phospholipids in randomly selected patients with essential hypertension. Fifty-seven newly diagnosed hypertensive patients were randomly divided into three groups. They received either single-blind B. mukul (1.5 g/d) or single-blind nifedipine (10 mg/d) double-blind therapy with nifedipine (10 mg/d) and B. mukul (1.5 g/d) for 6 weeks. These groups were compared with control subjects. On treatment with B. mukul, levels of systolic blood pressure, diastolic blood pressure, plasma total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglycerides, free fatty acids, and phospholipid levels were significantly reduced, and high-density lipoprotein cholesterol levels were significantly elevated, as compared with untreated hypertensive patients. Combined therapy with B. mukul and nifedipine was more beneficial than the treatment with B. mukul alone. Our study suggests that B. mukul may be an effective antihypertensive and hypolipidemic agent.