Mechanisms underlying the augmentation of phenylbiguanide and capsaicin induced cardiorespiratory reflexes by Mesobuthus tamulus venom

Phenylbiguanide (PBG) and capsaicin evoke cardiorespiratory reflexes utilizing two separate pathways. It is known that Indian Red Scorpion (Mesobuthus tumulus; MBT) venom augments PBG (5-HT₃) responses but, the effect of MBT venom on capsaicin (TRPV1)-induced response is not known. Therefore, the present study was undertaken to ascertain whether MBT venom also augments the capsaicin-induced reflex responses involving mechanisms similar to PBG. Experiments were performed on anaesthetized adult rats. Blood pressure, respiratory excursions and ECG were recorded. At the end of each experiment pulmonary water content was determined. PBG (10 μg/kg) produced hypotension, bradycardia and apnoea-bradypnoea. Capsaicin (10 μg/kg) also produced hypotension, bradycardia and apnoea-bradypnoea. MBT venom (100 μg/kg) augmented PBG as well as capsaicin-induced responses and produced pulmonary oedema (increased pulmonary water content). Prostaglandin synthase inhibitor (indomethacin; 10 mg/kg) blocked the venom-induced augmentation of PBG and capsaicin reflexes. Kinin synthase inhibitor (aprotinin; 6000 KIU) and guanylate cyclase (GC) inhibitor (methylene blue; 5 mg/kg) blocked the venom-induced augmentation of PBG response but not the capsaicin response. However, pulmonary oedema was blocked by these antagonists. Phosphodiesterase V inhibitor (sildenafil; 100 μg/kg) augmented the PBG response but not the capsaicin response, though pulmonary oedema was seen in both the groups. The present results indicate that MBT venom also augments the capsaicin-induced responses. The augmentation of capsaicin response involves PGs and pulmonary oedema-independent mechanisms whereas, the augmentation of PBG response involves kinin mediated GC-cGMP pathway and pulmonary oedema-dependent mechanisms.     

Evaluation of treatment of calcaneal fractures with a modified approach in a peripheral setting: a cost-effective model

Background

We present the results of open reduction and internal fixation of intra-articular calcaneal fractures with Kirschner wires with some modifications.

Material and methods

A longitudinal study was done on 37 patients who had fallen from certain heights; the study subjects were predominantly construction workers. Forty-seven fractures of the study subjects were treated using a modified approach that includes incision and some tips in operative technique. Details of modification and their evaluation on the basis of restoration of heel shape with special attention to the lateral wall, radiological assessment of Bohler’s angle, varus and valgus movement of the heel, pain while walking, patient satisfaction assessment upon return to pre-injury work are elaborated in this paper. Duration of study was from January 2000 to May 2011.

Results

The fractures healed well with good radiological and functional outcomes, and patients returned to pre-injury work status in 4–6 months.

Conclusion

The need to change to the Kocher approach for the treatment of calcaneal fracture with right-angled incision and elevation of the lateral flap is not necessary if the surgical tips showed in this paper are followed meticulously to achieve a good soft tissue outcome initially and, eventually, a good bony radiological and functional outcome. As implants used are very cheap and affordable to workers of low socioeconomic status, the authors have developed this method and presently believe that this method is best for all classes of patients with the said problem.     

Localized deferoxamine injection augments vascularity and improves bony union in pathologic fracture healing after radiotherapy

BackgroundMedically based efforts and alternative treatment strategies to prevent or remediate the corrosive effects of radiotherapy on pathologic fracture healing have failed to produce clear and convincing evidence of success. Establishing an effective pharmacologic option to prevent or treat the development of non-unions in this setting could have immense therapeutic potential. Experimental studies have shown that deferoxamine (DFO), an iron-chelating agent, bolsters vascularity and subsequently enhances normal fracture healing when injected locally into a fracture callus in long bone animal models. Since radiotherapy is known to impede angiogenesis, we hypothesized that the pharmacologic addition of DFO would serve to mitigate the effects of radiotherapy on new vessel formation in vitro and in vivo.Materials and MethodsIn vitro investigation of angiogenesis was conducted utilizing HUVEC cells in Matrigel. Endothelial tubule formation assays were divided into four groups: Control, Radiated, Radiated + Low-Dose DFO and Radiated + High-Dose DFO. Tubule formation was quantified microscopically and video recorded for the four groups simultaneously during the experiment. In vivo, three groups of Sprague–Dawley rats underwent external fixator placement and fracture osteotomy of the left mandible. Two groups received pre-operative fractionated radiotherapy, and one of these groups was treated with DFO after fracture repair. After 40 days, the animals were perfused and imaged with micro-CT to calculate vascular radiomorphometrics.ResultsIn vitro, endothelial tubule formation assays demonstrated that DFO mitigated the deleterious effects of radiation on angiogenesis. Further, high-dose DFO cultures appeared to organize within 2 h of incubation and achieved a robust network that was visibly superior to all other experimental groups in an accelerated fashion. In vivo, animals subjected to a human equivalent dose of radiotherapy (HEDR) and left mandibular fracture demonstrated quantifiably diminished μCT metrics of vascular density, as well as a 75% incidence of associated non-unions. The addition of DFO in this setting markedly improved vascularity as demonstrated with 3D angiographic modeling. In addition, we observed an increased incidence of bony unions in the DFO treated group when compared to radiated fractures without treatment (67% vs. 25% respectively).ConclusionOur data suggest that selectively targeting angiogenesis with localized DFO injections is sufficient to remediate the associated severe vascular diminution resulting from a HEDR. Perhaps the most consequential and clinically relevant finding was the ability to reduce the incidence of non-unions in a model where fracture healing was not routinely observed.     

Periodontal findings in patients with oral submucous fibrosis and comet assay of affected gingival epithelial cells

Background: Oral submucous fibrosis (OSF) involves large sections of population and is related to certain chewing practices that involve direct exposure of the gingiva to noxious chemicals and additives. The impact of such practices, although studied extensively in relation to the cheek mucosa, is not elucidated as far as gingival tissues are concerned. The possible DNA damage on affected gingiva is also one of the objectives of the present study. Methods: One hundred cases of individuals with OSF and 89 without OSF were examined for periodontal parameters and compared. Biopsies of gingival tissue from both categories were examined with conventional hematoxylin and eosin staining for epithelial, connective tissue, and inflammatory changes. Comet assay of epithelial cells obtained from scraping the gingival surface of both patients with OSF and control individuals was performed . Results: Patients with OSF had poorer oral hygiene and greater loss of attachment, probing depth, and recession compared with controls. Significant histopathologic changes in the form of loss of rete ridges with gingival epithelium reduced to a flattened surface was observed. All the patients with OSF showed comet cells in larger numbers. The controls also showed comet cells but in fewer numbers, and the number of individuals showing comet cells was significantly less. Conclusion: OSF showed significant changes in affected gingiva, and the presence of comet cells in all the patients with OSF is a significant indicator of possible pathognomonic developments.     

Optimized and Validated Stability Indicating RP-HPLC Method for Estimation of Nadolol

Pharmaceutical Chemistry Journal - A stability indicating RP-HPLC method for the determination of nadolol was developed and validated using Enable C18 (250 mm × 4.6 mm, 5 μm) column with...     

Molecular epidemiology of selected multidrug-resistant bacteria: a global report from the SENTRY Antimicrobial Surveillance Program

The SENTRY Antimicrobial Surveillance Program was initiated in 1997 as a global network for the longitudinal tracking of antimicrobial resistance and has incorporated a molecular typing protocol to detect and monitor emerging resistances in participant medical centers. Isolates with similar resistance profiles and patient demographics that were temporally related or those exhibiting emerging resistance phenotypes were routinely compared. Isolates were initially analyzed using the automated Riboprinter Microbial Characterization System (Qualicon, Inc., Wilmington, DE). Isolates with identical ribotype patterns were further characterized by pulsed field gel electrophoresis. During 2001, a total of 647 bacterial isolates were processed using this typing protocol; 36% were Staphylococcus aureus with multidrug-resistant, mupirocin- or quinupristin/dalfopristin-resistant phenotypes. Five ribotypes were predominant in this species with some occurring on more than one continent (184.5), whereas others were restricted to a single geographic region (893.2). Among S. aureus, 51 clusters demonstrating dissemination among patients were identified (31 medical centers). Twenty-three outbreaks/clusters were found among Enterobacteriaceae producing either extended-spectrum beta-lactamases or demonstrating resistance to fluoroquinolones. Carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. strains were also analyzed, some of which produced metallo-beta-lactamase enzymes. Clusters of carbapenem-resistant Acinetobacter were identified in Argentina and Israel, whereas metallo-beta-lactamase-producing P. aeruginosa epidemic strains were observed in Italy (three sites) and Brazil. The coupling of molecular epidemiologic investigations with global surveillance such as the SENTRY program adds significant value to participating medical centers and has proven to be effective in tracking changing trends and distribution of resistance genotypes both locally and globally.