Exacerbation of thrombotic events by diesel exhaust particle in mouse model of hypertension

Several epidemiological studies have shown that acute exposure to particulate air pollution is associated with increases in cardiovascular morbidity and mortality, and that these effects are especially exacerbated among individuals with pre-existing compromised cardiovascular function such as hypertension. This study was undertaken to determine the cardiovascular effect of diesel exhaust on TO mice made hypertensive by implanting osmotic minipump infusing angiotensin II or vehicle (control). On day 13, the animals were intratracheally instilled with either DEP (15 μg/mouse) or saline. 24 h later, pulmonary exposure to DEP had significantly decreased the systolic blood pressure (SBP) in hypertensive (HT) mice (P<0.01), but not in normotensive (NT) mice. The number of leukocytes and red blood cells, and the plasma interleukin 6 concentration in plasma, however, were not affected in any of the animals. The PaO? was decreased, and PaCO? increased in DEP-treated HT mice compared to NT mice treated with DEP (P<0.05). The number of circulating platelets was significantly increased in DEP-treated HT versus saline-treated HT and DEP-treated NT mice. Moreover, in NT mice, DEP exposure induced a prothrombotic effect in pial arterioles compared with saline-treated NT mice (P<0.05). Interestingly, in DEP-treated HT mice, the prothrombotic events were significantly aggravated compared with saline-treated HT and DEP-treated NT mice. The direct addition of DEP (0.1-1 μg/ml) to untreated mouse blood significantly induced in vitro platelet aggregation in a dose-dependent fashion, and these effects were more pronounced in blood of HT mice. In vitro exposure to DEP (0.25-1 μg/ml) led to activated intravascular coagulation, an effect that was confirmed by a shortening of both the activated partial thromboplastin time (aPTT) and the prothrombin time (PT). The effect of DEP on aPTT was potentiated in the plasma of HT mice. It can be concluded that the thrombotic events caused by DEP are exacerbated by hypertension in mice. Our findings, therefore, provide a possible plausible explanation for the cardiovascular morbidity and mortality accompanying urban air pollution.     

In silico prediction of monovalent and chimeric tetravalent vaccines for prevention and treatment of dengue fever

Reverse vaccinology method was used to predict the monovalent peptide vaccine candidate to produce antibodies for therapeutic purpose and to predict tetravalent vaccine candidate to act as a common vaccine to cover all the dengue virus serotypes. Envelope (E)-proteins of DENV-1-4 serotypes were used for vaccine prediction using NCBI, Uniprot/Swissprot, Swiss-prot viewer, VaxiJen V2.0, TMHMM, BCPREDS, Propred-1, Propred and MHC Pred. Eproteins of DENV-1-4 serotypes were identified as antigen from which T cell epitopes, through B cell epitopes, were predicted to act as peptide vaccine candidates. Each selected T cell epitope of E-protein was confirmed to act as vaccine and to induce complementary antibody against particular serotype of dengue virus. Chimeric tetravalent vaccine was formed by the conjugation of four vaccines, each from four dengue serotypes to act as a common vaccine candidate for all the four dengue serotypes. It can be justifiably concluded that the monovalent 9-mer T cell epitope for each DENV serotype can be used to produce specific antibody against dengue virus and a chimeric common tetravalent vaccine candidate to yield a comparative vaccine to cover any of the four dengue virus serotype. This vaccine is expected to be highly immunogenic against dengue fever.     

Treatment of Chronic Spontaneous Urticaria with a Single Dose of Omalizumab: A Study of Four Cases

Background:Chronic spontaneous urticaria (CSU) has a detrimental effect on patients’ emotional and physical quality of life. Omalizumab, an anti-immunoglobulin E humanized monoclonal antibody, has been shown to be very effective in the treatment of refractory chronic urticaria patients but may not be an economically viable option for all CSU patients. However, we present a case series where a single dose of omalizumab gave sustained relief of symptoms in patients with CSU, which may be an economical option.Aims:The aim of this study is to assess the efficacy of a single dose of omalizumab in the treatment of CSU. Materials and Methods: Four patients of CSU whose disease was not controlled with four times the licensed dose of tablet fexofenadine 180 mg were exhibited one subcutaneous injection of omalizumab and were followed up at 4 weekly intervals for 24 weeks for Weekly Urticaria Activity Score 7 (UAS7) and Dermatology Life Quality Index (DLQI).Results:A sharp decline in UAS7 and DLQI was documented in 7–10 days. The decline was maintained up to 16 weeks in one case and 20 weeks in the other three cases. Both the scores at the end of the follow-up period of 24 weeks were better than the pre-omalizumab scores.Conclusion:The results of this case series indicate the efficacy of a single-dose omalizumab in treating moderate to severe refractory CSU. Further studies are required to identify the minimum frequency of administering omalizumab to effectively control CSU. This would greatly reduce the cost of this novel therapy.     

Excision of carbuncle with primary split‐thickness skin grafting as a new treatment modality

Carbuncles are debilitating skin infections commonly seen in diabetic patients. Excision of these infective lesions leads to large defects that require prolonged hospital stay and repeated dressings with ensuing pain and bleeding. This study is an attempt to cover the wounds resulting from excision of carbuncle with primary skin grafting so as to decrease the hospital stay and frequency of dressings.     

Current status of percutaneous testicular biopsy for focal lesions

Objective

The purpose of this review is to evaluate the current role of percutaneous testicular biopsy in the diagnosis of focal testicular lesions.

Conclusion

Percutaneous testicular biopsy can be either fine needle aspiration biopsy or trucut core needle biopsy. It is a well-tolerated and effective procedure useful in small testicular lesions, multifocal lesions, hematological malignancies, and focal lesions in single testis.

     

Comparative Evaluation of Topical 10% Potassium Hydroxide and 30% Trichloroacetic Acid in the Treatment of Plane Warts

Background:Warts are benign proliferations of skin and mucosa caused by the human papillomavirus (HPV). Plane warts are caused by HPV types 3, 10, 28, and 41, occurring mostly in children and young adults. Among the treatment modalities, topical application of trichloroacetic acid (TCA) is age old. Potassium hydroxide (KOH) has a keratolytic effect on virus-infected cells. It is less irritating, less painful, less scar forming, and can be safely used in children too. Hence, it could be a better topical agent in the treatment of plane warts.Results:Statistically no significant difference (P = 0.07) was found between the objective therapeutic response to 10% KOH and 30% TCA at the end of study (12 weeks). However, subjective response to 10% KOH was better and statistically significant (P = 0.03). There was no recurrence of warts seen on follow-up for 3 months of complete responders in both the arms.Conclusion:10% KOH is found to be equally effective in the treatment of plane warts compared to 30% TCA with the advantage of faster onset of action and tendency of completely clearing warts with fewer side effects.     

Airway resistance, inflammation and oxidative stress following exposure to diesel exhaust particle in angiotensin II-induced hypertension in mice

Exposure to particulate matter is a risk factor for respiratory and cardiovascular diseases. However, the mechanisms underlying these effects are not well understood. Here, we compared the impact of diesel exhaust particles (DEP) on airway resistance, inflammation and oxidative stress in normal mice, or mice made hypertensive by implanting osmotic minipump infusing angiotensin II. On day 13 after the onset of infusion, angiotensin II induced significant increase in heart rate (P<0.05) and systolic blood pressure (P<0.0001). On the same day, mice were intratracheally instilled with either DEP (15 μg/mouse) or saline. Twenty-four hour later, the measurement of airway reactivity to methacholine (0-10mg/ml) in vivo by a forced oscillation technique showed a significant and dose dependent increase in airway resistance in normotensive mice exposed to DEP compared to those exposed to saline. In hypertensive mice, there was no difference in airway resistance in DEP versus saline exposed mice. However, following exposure to DEP, airway resistance significantly increased in normotensive versus hypertensive mice. Bronchoalveolar lavage (BAL) fluid analysis showed a significant increase in macrophage numbers in normotensive mice exposed to DEP compared to those exposed to saline, and to hypertensive mice exposed to DEP. Neutrophil numbers were significantly increased in both normotensive and hypertensive mice exposed to DEP compared with their respective control groups. Superoxide dismutase activity was significantly decreased following DEP exposure in both normotensive and hypertensive mice compared to their respective controls. However, total proteins, a marker for increase of epithelial permeability, and malondialdehyde, a reflection of lipid peroxidation, were only increased in normotensive mice exposed to DEP. Therefore, our data suggest that DEP do not aggravate airway resistance and inflammation in angiotensin II-induced hypertensive mice. On the contrary, at the dose of DEP and time point investigated, airway resistance, inflammation and oxidative stress are increased in normotensive compared to hypertensive mice.     

Shrimp lectin (Md-Lec) conjugated copper sulfide nanoparticles enhance the elimination of aquatic pathogens in infected Nile tilapia (Oreochromis niloticus)

Lectins are known for their ability to bind to cell surface glycans, and are useful to develop a glycan-targeted drug delivery system. This study aimed to evaluate the capacity of pectin capped copper sulfide nanoparticles (pCuS NPs) to modulate the antibacterial activity of a lectin, Md-Lec, purified from the shrimp, Metapenaeus dobsoni. Fluorescence spectroscopy revealed that Md-Lec has the ability to form a complex with pCuS NPs. Haemagglutination assay showed that the carbohydrate binding site of the lectin was preserved even after complexing with pCuS. The minimum inhibitory concentrations (MICs) obtained for Md-Lec and pCuS NPs against the tested aquatic pathogens were 50 μg ml⁻¹ and 12.5 μM, respectively. Interestingly, the MIC of Md-Lec–pCuS NPs complex was four fold lower than that of pCuS, which was attributed to the bacterial cell surface glycan recognization activity of Md-Lec. Zone of inhibition assay showed that the zone size was highest for the lectin conjugated nanoparticles. Mechanistic study revealed that Md-Lec–pCuS NPs affect the bacterial membrane integrity and produce a large volume of reactive oxygen species to kill the bacteria. The practical aspect of using this lectin–pCuS NPs complex was evaluated by treating bacteria infected Nile tilapia (Oreochromis niloticus). The bacterial load was much less in the lectin–pCus NPs complex treated fish; moreover, the fish fully recovered from the infection. It was concluded that the conjugate of antibacterial lectin and NPs is more effective than the individual components.

Synthesis of Md-Lec-pCuSNPs and its enhanced in vitro and in vivo antibacterial activity.