Antimicrobial activity of three medicinal plants (Artemisia indica, Medicago falcate and Tecoma stans)

Background: Artemisia indica, Medicago falcata and Tecoma stans are traditionally being use for medicinal purposes in Pakistan. Present study was designed to check in-vitro efficacy of these plants against selected bacterial and fungal strains.Methodology: Chloroform, butanol, ethyl acetate and n-hexane extracts of these plants were used for antimicrobial screening. Antibacterial activity was tested against four pathogenic bacterial strains i.e. Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Staphylococcus aureus while antifungal activity was tested against four fungal strains i.e. Aspergillus flavus, Aspergillus niger, Aspergillus fumigatus and Fusarium solani.Results: Chloroform, butanol and ethyl acetate extracts of Artemisia indica, Medicago falcata and Tecoma stans showed high inhibitory activities (between 15-20 mm) against E. coli, P. aeruginosa and S. aureus. However, all extracts of Artemisia indica showed inhibitory activities (12-14 mm) against Salmonella typhi. As antifungal activities, the n-Hexane and chloroform extracts of Artemisia indica have completely inhibited the growth of Aspergillus flavus and Fusariun solani, respectively. Ethyl acetate and butanol extract of Medicago falcata completely inhibited Fusarium solani and Aspergillus fumigates, respectively. The n-hexane extract of Tecoma stans completely inhibited Fusarium solani, while its ethyl acetate extract shows excellent activity against Aspergillus niger.Conclusions: These findings provide scientific evidence of traditional use of medicinal plants and also indicate the potential of these plants for the development of antimicrobial agents.Key words: Medicinal Plants, Traditional uses, phytochemical effects, Antimicrobial activity

Genetic background influences tumour development in heterozygous Men1 knockout mice

Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder caused by MEN1 germline mutations, is characterised by parathyroid, pancreatic and pituitary tumours. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP), a milder condition causing hyperparathyroidism only. Identical mutations can cause either MEN1 or FIHP in different families, thereby implicating a role for genetic modifiers in altering phenotypic expression of tumours. We therefore investigated the effects of genetic background and potential for genetic modifiers on tumour development in adult Men1+/- mice, which develop tumours of the parathyroids, pancreatic islets, anterior pituitary, adrenal cortex and gonads, that had been backcrossed to generate C57BL/6 and 129S6/SvEv congenic strains. A total of 275 Men1+/- mice, aged 5–26 months were macroscopically studied, and this revealed that genetic background significantly influenced the development of pituitary, adrenal and ovarian tumours, which occurred in mice over 12 months of age and more frequently in C57BL/6 females, 129S6/SvEv males and 129S6/SvEv females, respectively. Moreover, pituitary and adrenal tumours developed earlier, in C57BL/6 males and 129S6/SvEv females, respectively, and pancreatic and testicular tumours developed earlier in 129S6/SvEv males. Furthermore, glucagon-positive staining pancreatic tumours occurred more frequently in 129S6/SvEv Men1+/- mice. Whole genome sequence analysis of 129S6/SvEv and C57BL/6 Men1+/- mice revealed >54,000 different variants in >300 genes. These included, Coq7, Dmpk, Ccne2, Kras, Wnt2b, Il3ra and Tnfrsf10a, and qRT-PCR analysis revealed that Kras was significantly higher in pituitaries of male 129S6/SvEv mice. Thus, our results demonstrate that Kras and other genes could represent possible genetic modifiers of Men1

Carbonic anhydrase inhibitors. Inhibition of human tumor-associated isozymes IX and cytosolic isozymes I and II with some 1,3,4-oxadiazole-thiols.

A series of chiral 1,3,4-oxadiazole-5-thiols incorporating 2-substituted-benzenesulfonamide moieties has been prepared from amino acids, via the ester and carbohydrazide intermediate, followed by cyclization with carbon disulfide. Some of these compounds have been investigated for the inhibition of three physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human cytosolic hCA I and II, and the human, transmembrane, tumor-associated isozyme hCA IX. All these compounds showed weak (millimolar) affinity for the three isozymes, except two carbohydrazides and two heterocyclic thiols which selectively inhibited the tumor-associated isozyme with inhibition constants around 10 microM. Such compounds constitute interesting lead molecules for the possible design of CA IX-selective inhibitors

Synthesis and antimalarial activity of novel chiral and achiral benzenesulfonamides bearing 1, 3, 4-oxadiazole moieties.

A series of new benzenesulfonamides, most of which are chiral, incorporating 1, 3, 4-oxadiazole and amino acid moieties have been synthesized. Some of these compounds were screened for antimalarial activity and also evaluated for their ability to inhibit hem polymerization. The electrophoretic analysis indicated that one compound was effective in inhibiting the degradation of hemoglobin. The synthesized compounds were tested in mice infected with Plasmodium berghei. These derivatives have the potential for the development of novel antimalarial lead compounds

Subcutaneous dissociative conscious sedation (sDCS) an alternative method for airway regional blocks: a new approach

<p>Abstract</p> <p>Background</p> <p>Predicted difficult airway is a definite indication for awake intubation and spontaneous ventilation. Airway regional blocks which are commonly used to facilitate awake intubation are sometimes impossible or forbidden. On the other hand deep sedation could be life threatening in the case of compromised airway.</p> <p>The aim of this study is evaluating "Subcutaneous Dissociative Conscious Sedation" (sDCS) as an alternative method to airway regional blocks for awake intubation.</p> <p>Methods</p> <p>In this prospective, non-randomized study, 30 patients with predicted difficult airway (laryngeal tumors), who were scheduled for direct laryngoscopic biopsy (DLB), underwent "Subcutaneous Dissociative Conscious Sedation" (sDCS) exerted by intravenous fentanyl 3-4ug/kg and subcutaneous ketamine 0.6-0.7 mg/kg. The tongue and pharynx were anesthetized with lidocaine spray (4%<b>)</b>. 10 minutes after a subcutaneous injection of ketamine direct laryngoscopy was performed. Extra doses of fentanyl 50-100 ug were administered if the patient wasn't cooperative enough for laryngoscopy.</p> <p>Patients were evaluated for hemodynamic stability (heart rate and blood pressure), oxygen saturation (Spo₂), patient cooperation (obedient to open the mouth for laryngoscopy and the number of tries for laryngoscopy), patient comfort (remaining moveless), hallucination, nystagmus and salivation (need for aspiration before laryngoscopy).</p> <p>Results</p> <p>Direct laryngoscopy was performed successfully in all patients. One patient needed extra fentanyl and then laryngoscopy was performed successfully on the second try. All patients were cooperative enough during laryngoscopy. Hemodynamic changes more than 20% occurred in just one patient. Oxygen desaturation (spo₂< 90%) didn't occur in any patient.</p> <p>Conclusions</p> <p>Subcutaneous Dissociative Conscious Sedation (sDCS) as a new approach to airway is an acceptable and safe method for awake intubation and it can be suggested as a noninvasive substitute of low complication rate for regional airway blocks.</p> <p>Registration ID in IRCT</p> <p>IRCT201012075333N1</p

Anomalous rotational-alignment in N=Z nuclei and residual neutron-proton interaction

Recent experiments have demonstrated that the rotational-alignment for the $N=Z$ nuclei in the mass-80 region is considerably delayed as compared to the neighboring $N \ne Z$ nuclei. We investigate whether this observation can be understood by a known component of nuclear residual interactions. It is shown that the quadrupole-pairing interaction, which explains many of the delays known in rare-earth nuclei, does not produce the substantial delay observed for these $N=Z$ nuclei. However, the residual neutron-proton interaction which is conjectured to be relevant for $N=Z$ nuclei is shown to be quite important in explaining the new experimental data.Comment: 4 pages, 3 figures, final version accepted by Phys. Rev. C as a Rapid Communicatio

Multi-Phonon γ\gamma-Vibrational Bands and the Triaxial Projected Shell Model

We present a fully quantum-mechanical, microscopic, unified treatment of ground-state band and multi-phonon $\gamma$-vibrational bands using shell model diagonalization with the triaxial projected shell model. The results agree very well with data on the g- and $\gamma$-band spectra in $^{156-170}$Er, as well as with recently measured $4^+$ 2-phonon $\gamma$-bandhead energies in $^{166}$Er and $^{168}$Er. Multi-phonon $\gamma$-excitation energies are predicted.Comment: 4 pages, 4 figures, submitted to Phys. Lett.

PCR array and protein array studies demonstrate that IL-1β (interleukin-1β) stimulates the expression and secretion of multiple cytokines and chemokines in human adipocytes

The role of IL-1β in regulating the expression and secretion of cytokines and chemokines by human adipocytes was examined. Adipocytes were incubated with human IL-1β for 4 or 24 h. The expression of a panel of 84 cytokine/chemokine genes was probed using PCR arrays. IL-1β stimulated the expression of >30 cytokine/chemokine genes on the arrays; 15 showed >100-fold increases in mRNA at 4 or 24 h including CSF3, CXCL1, CXCL2, CXCL12 and IL8. CSF3 exhibited a 10,000-fold increase in mRNA at 4 h. ADIPOQ was among the genes whose expression was inhibited. Protein arrays were used to examine the secretion of cytokines/chemokines from adipocytes. IL-1β stimulated the secretion of multiple cytokines/chemokines including MCP-1, IL-8, IP-10, MIP-1α and MCP-4. The most responsive was IP-10, which exhibited a 5,000-fold increase in secretion with IL-1β. IL-1β is likely to play a substantial role in stimulating the inflammatory response in human adipocytes in obesity

Phenyl Bis-Sulfonamide Keap1-Nrf2 Protein–Protein Interaction Inhibitors with an Alternative Binding Mode

Inhibitors of Kelch-like ECH-associated protein 1 (Keap1) increase the activity of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) by stalling its ubiquitination and degradation. This enhances the expression of genes encoding proteins involved in drug detoxification, redox homeostasis, and mitochondrial function. Nrf2 activation offers a potential therapeutic approach for conditions including Alzheimer’s and Parkinson’s diseases, vascular inflammation, and chronic obstructive airway disease. Non-electrophilic Keap1-Nrf2 protein–protein interaction (PPI) inhibitors may have improved toxicity profiles and different pharmacological properties to cysteine-reactive electrophilic inhibitors. Here, we describe and characterize a series of phenyl bis-sulfonamide PPI inhibitors that bind to Keap1 at submicromolar concentrations. Structural studies reveal that the compounds bind to Keap1 in a distinct “peptidomimetic” conformation that resembles the Keap1-Nrf2 ETGE peptide complex. This is different to other small molecule Keap1-Nrf2 PPI inhibitors, including bicyclic aryl bis-sulfonamides, offering a starting point for new design approaches to Keap1 inhibitors