Combined in vitro and in silico approach to evaluate the inhibitory potential of an underutilized allium vegetable and its pharmacologically active compounds on multidrug resistant Candida species.

Candida infections and related mortality have become a challenge to global health. Nontoxic and natural bioactive compounds from plants are regarded as promising candidates to inhibit these multidrug resistant strains. In the present study, in vitro assays and in silico molecular docking approach was combined to evaluate the inhibitory effect of crude extracts from Allium ampeloprasum and its variety A. porrum on Candida pathogens. Phytochemical screening revealed the presence of phenolic acids and flavonoids in higher quantity. Spectral studies of the extracts support the presence of phenols, flavonoids and organosulfur compounds. Aqueous extract of A. ampeloprasum showed a total antioxidant capacity of 68 ± 1.7 mg AAE/ g and an IC50 value of 0.88 ± 2.1 mg/ml was obtained for DPPH radicals scavenging assay. C. albicans were highly susceptible (19.9 ± 1.1 mm) when treated with aqueous A. ampeloprasum extract. Minimum inhibitory concentrations were within the range of 19-40 µg/ml and the results were significant (p ≤ 0.05). In silico molecular docking studies demonstrated that bioactive phytocompounds of A. ampeloprasum and A. porrum efficiently interacted with the active site of Secreted aspartyl proteinase 2 enzyme that is responsible for the virulence of pathogenic yeasts. Rosmarinic acid and Myricetin exhibited low binding energies and higher number of hydrogen bond interactions with the protein target. Thus the study concludes that A. ampeloprasum and A. porrum that remain as underutilized vegetables in the Allium genus are potential anti-candida agents and their pharmacologically active compounds must be considered as competent candidates for drug discovery.

Identification of novel bioactive molecules from garlic bulbs: A special effort to determine the anticancer potential against lung cancer with targeted drugs.

Garlic (Allium sativum L.), is a predominant spice, which is used as an herbal medicine and flavoring agent, since ancient times. It has a rich source of various secondary metabolites such as flavonoids, terpenoids and alkaloids, which have various pharmacological properties. Garlic is used in the treatment of various ailments such as cancer, diabetes and cardiovascular diseases. The present study aims to explore the plausible mechanisms of the selected phytocompounds as potential inhibitors against the known drug targets of non-small-cell lung cancer (NSCLC). The phytocompounds of garlic were identified by gas chromatography-mass spectrometry (GC-MS) technique. Subsequently, the identified phytocompounds were subjected to molecular docking to predict the binding with the drug targets, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and group IIa secretory phospholipase A2 (sPLA2-IIA). Molecular dynamics is used to predict the stability of the identified phytocompounds against NSCLC drug targets by refining the intermolecular interactions formed between them. Among the 12 phytocompounds of garlic, three compounds[1,4-dimethyl-7-(1-methylethyl)-2-azulenyl]phenylmethanone, 2,4-bis(1-phenylethyl)-phenol and 4,5-2 h-oxazole-5-one,4-[3,5-di-t-butyl-4-methoxyphenyl] methylene-2-phenyl were identified as potential inhibitors, which might be suitable for targeting the different clinical forms of EGFR and dual inhibition of the studied drug targets to combat NSCLC. The result of this study suggest that these identified phytocompounds from garlic would serve as promising leads for the development of lead molecules to design new multi-targeting drugs to address the different clinical forms of NSCLC.

Extragastrointestinal stromal tumour of the abdominal wall - a case report.

Stromal tumours occurring in areas other than the GastroIntestinal Tract (GIT) are known as Extra GastroIntestinal Stromal Tumours (EGISTs). They usually arise in the mesentery, omentum or retroperitoneum, while EGISTs which occur in the abdominal wall are very rare. Both gastrointestinal stromal tumours (GISTs) and EGISTs are histologically and immunophenotypically similar. We are reporting a case of EGIST, which occurred in the anterior abdominal wall in a twenty five-year-old female patient. The tumour was present in the right loin and imaging studies suggested that it was a desmoid tumour. It was surgically excised by doing an abdominal wall mesh repair. The histological examinations revealed a tumour with spindle cell morphology, with <2 mitoses per 50 High Power Field (HPF) and no necrosis, with tumour free margins. Immunohistochemistry was strongly positive for CD117 and Smooth Muscle Actin (SMA), while it was negative for ß-catenin and S100. The patient is well post operatively and is on close follow up. EGISTs should be considered in the differential diagnosis of mesenchymal tumours which occur in the abdominal wall, inspite of their rarity, as the high risk patients may need Imatinib chemotherapy.

Airway vascular reactivity and vascularisation in human chronic airway disease.

Altered bronchial vascular reactivity and remodelling including angiogenesis are documented features of asthma and other chronic inflammatory airway diseases. Expansion of the bronchial vasculature under these conditions involves both functional (vasodilation, hyperperfusion, increased microvascular permeability, oedema formation, and inflammatory cell recruitment) and structural changes (tissue and vascular remodelling) in the airways. These changes in airway vascular reactivity and vascularisation have significant pathophysiological consequences, which are manifest in the clinical symptoms of airway disease. Airway vascular reactivity is regulated by a wide variety of neurotransmitters and inflammatory mediators. Similarly, multiple growth factors are implicated in airway angiogenesis, with vascular endothelial growth factor amongst the most important. Increasing attention is focused on the complex interplay between angiogenic growth factors, airway smooth muscle and the various collagen-derived fragments that exhibit anti-angiogenic properties. The balance of these dynamic influences in airway neovascularisation processes and their therapeutic implications is just beginning to be elucidated. In this review article, we provide an account of recent developments in the areas of vascular reactivity and airway angiogenesis in chronic airway diseases.

Protective effect of vilva juice on glycoconjugate levels in experimentally induced constipation in rats.

Efficacy of vilva, a polyherbal formulation was evaluated in morphine induced constipated rats. Vilva juice, at a dose of 1.5 ml/100 g body wt was given orally for a period of 7 days. Morphine sulfate was injected to induce constipation on 8th day, 45 min before the experiments. Protein bound glycoconjungates were estimated in intestinal tissue. Altered levels of glycoconjugates were maintained at near normalcy when pretreated with vilva juice in morphine induced rats. Histological changes were observed in the colon tissue. The damage to crypts of Liberkunn in constipated rats were found to be reduced in vilva pretreated rats. Vilva, thus, offered significant protection against morphine induced constipation by way of augmenting mucus secretion.

Short course chemotherapy for tuberculosis in children.

In order to determine the efficacy of short course chemotherapy (SCC) for tuberculosis in children, 83 newly diagnosed cases in children < 12 years old were given SCC and were prospectively followed for 1-3 years. Seventy-one cases were treated for 6-9 months as they had mild to moderate involvement. Twelve cases were treated for 12 months as they had meningitis (7), disseminated tuberculosis (2), or miliary tuberculosis (3). The results showed that none of the children, at the end of follow up, showed evidence of active tuberculosis. All children tolerated the drugs well, with side effects noticed being mild, namely transient hepatitis (4), vomiting (1), and skin rash (1). It is suggested that SCC for 6-9 months using isoniazid (INH) and rifampicin along with other drugs when necessary is highly effective in most cases of tuberculosis in children and has several advantages over conventional chemotherapy of 18 months or longer duration.

Empyema in infancy and childhood.

A study of 108 cases of empyema during 18 months period showed the incidence of empyema to be 2.17%. Staph. aureus (17.6%) was the common causative organism. Response to a combination of cloxacillin and gentamicin was better than that of crystalline penicillin and gentamicin. Only 30.3% cases needed intercostal drainage for more than 2 weeks. Almost 43% cases could be discharged by 3-4 weeks after hospitalisation and 38.1% by 30-57 days. The mortality rate was 12.1%. Among the survivors, excluding 8 children who left against medical advice, all had complete recovery excepting one child in whom AFB was isolated and who developed bronchiectasis and recurrent hemoptysis, inspite of antituberculous treatment. Age of the child, antibiotic combination given and nutritional status appear to be the main factors influencing the recovery and prognosis.

Mechanism of immunosuppression in leprosy: presence of suppressor factor(s) from macrophages of lepromatous patients

Human peripheral blood mononuclear cell proliferation induced by Mycobacterium leprae could...

Role of carbamazepine in reducing polypharmacy in epilepsy.

Carbamazepine was given to 152 patients who were receiving multiple drug therapy for uncontrolled seizures. The age range was 3 to 57 years. The mean average duration of epilepsy and carbamazepine therapy was 7.6 years and 19 months respectively. The conclusions are: (i) Carbamazepine is effective in reducing the multiple drug therapy while still maintaining better control of epilepsy. (ii) Carbamazepine by reducing polypharmacy in epilepsy and probably by the relative lack of sedative action is effective in improving school or work performances. (iii) Carbamazepine is a safe antiepileptic drug.