Molecular Dynamics Simulation of Β-Melanotropin Stimulating Hormone (Β-MSH) Docked Onto the Receptor MC4R.

Melanocortin system is composed of four peptide hormones known as α, β, γ and adrenocorticotropic hormone (ACTH), derived from post-translational cleavage of a polypeptide precursor ‘proopiomelanocortin (POMC)’. Among these hormones; β-melanotropin stimulating hormone (β-MSH), an 18 amino acid residue peptide fragment is an important hormone as it is involved in activation of MC4R to induce lean phenotype ‘balance between energy intake and energy expenditure’. In addition to this, MC4R is also involved in the modulation of erectile function, including the spinal cord and pelvic ganglion of rats and the penis of both rats and humans, providing an anatomical basis for melanocortin effects on sexual function. MC4R is one of the five melanocortin receptors (MC1R–MC5R) which have been characterized with tissue-specific expression patterns and different binding affinities for each of the melanocortin hormones to regulate various biological functions. In the present work, 3D models of MC4R and β-MSH have been predicted, followed by docking and molecular dynamics simulation. While the 3D model of MC4R receptor has been predicted through threading approach, structure of β- MSH was built based on ab initio technique. The β-MSH model was later successfully docked onto the MC4R protein. Molecular dynamics (MD) simulation for 15 ns was used to compute the electrostatic solvation energy as well as binding energy between MC4R with β-MSH model under implicit solvent conditions.

Response of aerobic rice to Piriformospora indica.

Rice cultivation under aerobic condition not only saves water but also opens up a splendid scope for effective application of beneficial root symbionts in rice crop unlike conventional puddled rice cultivation where water logged condition acts as constraint for easy proliferation of various beneficial soil microorganisms like arbuscular mycorrhizal (AM) fungi. Keeping these in view, an in silico investigation were carried out to explore the interaction of hydrogen phosphate with phosphate transporter protein (PTP) from P. indica. This was followed by greenhouse investigation to study the response of aerobic rice to Glomus fasciculatum, a conventional P biofertilizer and P. indica, an alternative to AM fungi. Computational studies using ClustalW tool revealed several conserved motifs between the phosphate transporters from Piriformospora indica and 8 other Glomus species. The 3D model of PTP from P.indica resembling “Mayan temple” was successfully docked onto hydrogen phosphate, indicating the affinity of this protein for inorganic phosphorus. Greenhouse studies revealed inoculation of aerobic rice either with P. indica, G. fasciculatum or both significantly enhanced the plant growth, biomass and yield with higher NPK, chlorophyll and sugar compared to uninoculated ones, P. indica inoculated plants being superior. A significantly enhanced activity of acid phosphatase and alkaline phosphatase were noticed in the rhizosphere soil of rice plants inoculated either with P. indica, G. fasciculatum or both, contributing to higher P uptake. Further, inoculation of aerobic rice plants with P. indica proved to be a better choice as a potential biofertilizer over mycorrhiza.

Molecular modeling of 2-nitropropane dioxygenase domain of Mycobacterium tuberculosis H37Rv and docking of herbal ligands.

The 3D structure of enoyl reductase (ER) domain generated by the SWISS MODEL server contains the 2-nitropropane dioxygenase (2NPD) structure displaying the TIM barrel fold. Though TIM barrel fold is made up of both main and inserted domains, in our study, we could only predict the structure of the main domain, which had central barrel of eight β-strands surrounded by eight α-helices. Superimposition of the 2NPD region of ER domain of Mycobacterium tuberculosis H37Rv on to the corresponding region of 2UVA_G revealed a good structural alignment between the two, suggesting this template to be a good structural homologue. Among various herbal ligands that were screened as inhibitors, daucosterol was found to bind in closest proximity to the flavin mono nucleotide (FMN) binding site with the lowest docking energy

Evaluation of safety and efficacy of azithromycin in lower respiratory tract infections (LRTI)

Azithromycin was given to 55 cases of lower respiratory tract infections in the doses of 500 mg on day 1, followed by 250 mg on days 2-5. It produced bacteriological cure in 70.8% patients and clinical cure or improvement in 69.09% of patients. 4.27% of patients had throat colonisation with new organisms, of which 9.09% needed a second antibiotic. The drug was well tolerated and minor side effects were noted. Gastrointestinal disturbances (16.36%) headache and giddiness (14.55%), rash (3.64%) were the noted side effects. Reduction of platelet count by 50% occurred in 12.29% of the cases compared to 0.2% reported earlier. But this thrombocytopenia was clinically not significant, as it did not cause any symptoms.

A new role for vitamin D: cholecalciferol promotes dermal wound strength and re-epithelization.

Vitamin D endocrine system is a potent regulator of cell growth and maturation. Vitamin D3 modulates growth kinetics of many cells and produces divergent actions. Keeping this in view, cholecalciferol is evaluated for its actions on dermal wound healing in Wistar rats. Intraperitonial cholecalciferol at 5, 10, 15 IU/g body weight doses produces increases in wound breaking strength and promotes epithelization significantly. Results suggest that there is some biological role for vitamin D endocrine system, ir wound repair. A clear understanding of this role of vitamin D3 may define new avenues in wound medication.

Wound healing profile of topical xylocaine preparations in rodents.

Local anesthetics are commonly used for alleviating pain in many clinical conditions associated with wound. Present study is undertaken to unravel the implications of two xylocaine preparations on dermal wound repair in albino rats. Application of xylocaine either as jelly or ointment significantly reduced skin wound breaking strength and promoted re-epithelization. While bases of xylocaine jelly and ointment had no action on skin wound breaking strength but enhanced re-epithelization. Current findings, suggest that prior knowledge of the effects of substances incorporated in topical preparations on wound repair is important for their judicious use and selection of preparation in relevant clinical conditions.

Effect of histamine on wound healing.

Using incision, excision and dead space wound models in rats, a study was conducted on the effect of histamine on wound healing. Exogenous histamine given either ip or locally was without any effect. Semicarbazide as (histamine synthesis inhibitor) suppressed healing process (breaking strength of skin incision wound), decreased breaking strength and hydroxyproline content of granulation tissue and delay in period of epithelization. On the other hand compound 48/80 (a promoter of histamine forming capacity) was found to promote wound healing. Exogenous histamine (topical) reversed the anti-healing effect of semicarbazide on incision and excision wounds.

Effects of antihistamines on wound healing.

Role of antihistamines (H1 and H2 blockers) in wound healing by utilizing incision and dead space wound models in albino rats was investigated. H1 blockers (mepyramine and promethazine) were found to decrease breaking strength of 10 day old dermal incision wounds and collagen content (as hydroxyproline) and breaking strength of granulation tissue harvested over tubular implant. On the other hand H2 blockers (Cimetidine and ranitidine) did not alter the above parameters. The findings that H1 blockers suppress healing implicate H1 receptors in alleged prohealing effect of histamine, and suggest clinical evaluation of these agents for suppression of overhealing states like keloid, adhesions and strictures.

A simple method to quantify maturation of wound collagen.

While investigating the effect of NSAIDs and Zn(II) (NSAIDs)2 complexes on healing of dead space wounds we found that both NSAIDs and Zn(II) (NSAIDs)2 reduced collagen content to a comparable extent yet only NSAIDs reduced breaking strength (BS) of wounds. Since collagen content and maturation are the two important determinants of BS it was obvious that only NSAIDs reduced maturation. A simple method to assess the extent of maturation in available collagen is being reported in the present study. While all NSAIDs significantly reduced the maturation of collagen, Zn(II) (NSAIDs)2 complexes per se did not affect the maturation of collagen of 10-day old. Though, chronologically, granulation tissues obtained from both the treated groups were 10-day old, maturation-wise the age of NSAIDs and Zn(II) (NSAIDs)2 treated granulation was 6 and 12 days respectively.

Comparative evaluation of tolmetin & tolmetin-zinc on wound-repair & inflammation.

In view of the reported healing-suppressant activity of some NSAIDs and absence of this adverse effect in their zinc-complexes, tolmetin (Tol), a recently introduced NSAID and its zinc-complex (Tol-Zn) were compared for their wound healing and antiinflammatory profiles in male albino rats. Tolmetin-zinc (Tol-Zn) significantly reversed (P less than 0.01) the suppressant effect of Tol on gain in breaking strength of skin incisions and dead space wounds (breaking strength, g: for control, Tol and Tol-Zn were: 313 +/- 7, 250 +/- 11, 294 +/- 16 in skin wounds; 244 +/- 7, 137 +/- 18, 195 +/- 16 in dead space wounds). Tol-Zn shared the significant (P less than 0.001) suppressant effect of Tol on granuloma formation (granuloma weight, mg: control - 69 +/- 3, Tol - 36 +/- 3.03, Tol-Zn - 37 +/- 2.75) and its collagen content (total hydroxyproline per tissue, microgram: control - 1955 +/- 55, Tol - 1400 +/- 200, Tol-Zn - 1410 +/- 150). Rat paw edema induced by carrageenin was significantly (P less than 0.001) reduced by Tol as well as Tol-Zn. In the chronic model both the agents suppressed significantly (P less than 0.001) granuloma formation by 50 per cent. Zinc sulphate by itself reduced the rat paw edema by 39 per cent (P less than 0.02) and did not affect the other parameters. Zinc-complex appears to be an improved version of tolmetin as an antiinflammatory agent with no adverse effect on the healing process. Tolmetin-zinc promotes gain in breaking strength, not by increasing the collagen content, but by favouring better maturation of available collagen at the wound site.

Effects of procoagulants on wound healing.

As blood coagulation is a prelude for wound healing, a systemic haemocoagulant (Botropase) and local procoagulants (thrombin and fibrin) were evaluated on physical (wound breaking strength, wound half-closure time and period of epithelization), biochemical (granuloma-hydroxyproline and hexosamine) and histological attributes of healing wounds in albino rats. Botropase prompted all phases of tissue repair. Thrombin delayed wound contraction whereas fibrin had no discernable action. The findings that procoagulants modify healing process has bearing on their surgical use.