Muhammad Imran Qadir

Beneficial effects of lactic acid bacteria on human beings

Lactic acid bacteria are a diverse group of bacteria that produce lactic acid as their major fermented product. Most of them are normal flora of human being and animals and produce myriad beneficial effects for human beings include, alleviation of lactose intolerance, diarrhea, peptic ulcer, stimulation of immune system, antiallergic effects, antifungal actions, preservation of food, and prevention of colon cancer. This review highlights the potential species of Lactic acid bacteria responsible for producing these effects. It has been concluded that lactic acid bacteria are highly beneficial microorganisms for human beings and are present abundantly in dairy products so their use should be promoted for good human health.

Inhibitors of Apoptotic Proteins: New Targets for Anticancer Therapy

Inhibitors of apoptotic proteins (IAPs) can play an important role in inhibiting apoptosis by exerting their negative action on caspases (apoptotic proteins). There are eight proteins in this family: NAIP/BIRC1/NLRB, cellular IAP1 (cIAP1)/human IAP2/BIRC2, cellular IAP2 (cIAP2)/human IAP1/BIRC3, X‐linked IAP (XIAP)/BIRC4, survivin/BIRC5, baculoviral IAP repeat (BIR)‐containing ubiquitin‐conjugating enzyme/apollon/BIRC6, livin/melanoma‐IAP (ML‐IAP)/BIRC7/KIAP, and testis‐specific IAP (Ts‐IAP)/hILP‐2/BIRC8. Deregulation of these inhibitors of apoptotic proteins (IAPs) may push cell toward cancer and neurodegenerative disorders. Inhibitors of apoptotic proteins (IAPs) may provide new target for anticancer therapy. Drugs may be developed that are inhibiting these IAPs to induce apoptosis in cancerous cells.

Effect of degree of cross-linking on swelling and drug release behaviour of poly(methyl methacrylate-co-itaconic acid) [P(MMA/IA)] hydrogels for site specific drug delivery

In this research work the effect of the degree of cross-linking on swelling and drug release behavior of poly (methyl methacrylate-co-itaconic acid) [P(MMA/IA)] hydrogels for site specific drug delivery was studied. In MMA/IA polymer, considering both dynamic and equilibrium swelling of monomeric ratios i.e. 70:30 and 80:20, the degrees of cross-linking of 0.15, 025 and 0.30 mol% seem better than 0.35 and 0.45 mol%. For all degrees of cross-linking, the 70:30 proportions seem suitable for achieving the required objectives, because in these samples, swelling was very high at higher pH values and absent at low pH values as compared with 80:20 proportions. MMA/IA copolymer was also examined in vitro for their suitability for lactulose delivery to the colon. It was observed that the MMA/IA polymer is suitable for delivering the drug above pH 6. In this polymer, whatever the degree of cross-linking, limited drug released at pH 1.2, 5.5 and significant at pH 6.5 but maximum release was at pH 7.

Orally disintegrating films: A modern expansion in drug delivery system.

Over the past few decades, tendency toward innovative drug delivery systems has majorly increased attempts to ensure efficacy, safety and patient acceptability. As discovery and development of new chemical agents is a complex, expensive and time consuming process, so recent trends are shifting toward designing and developing innovative drug delivery systems for existing drugs. Out of those, drug delivery system being very eminent among pediatrics and geriatrics is orally disintegrating films (ODFs). These fast disintegrating films have superiority over fast disintegrating tablets as the latter are associated with the risks of choking and friability. This drug delivery system has numerous advantages over conventional fast disintegrating tablets as they can be used for dysphasic and schizophrenic patients and are taken without water due to their ability to disintegrate within a few seconds releasing medication in mouth. Various approaches are employed for formulating ODFs and among which solvent casting and spraying methods are frequently used. Generally, hydrophilic polymers along with other excipients are used for preparing ODFs which allow films to disintegrate quickly releasing incorporated active pharmaceutical ingredient (API) within seconds. Orally disintegrating films have potential for business and market exploitation because of their myriad of benefits over orally disintegrating tablets. This present review attempts to focus on benefits, composition, approaches for formulation and evaluation of ODFs. Additionally, the market prospect of this innovative dosage form is also targeted.

HIV fusion inhibitors

Drugs based on amino acid sequence of Heptad Repeats of gp41 of HIV have been explored in search of anti‐HIV drugs acting by inhibition of the gp41 6‐helix formation and subsequent cellular infection. These are classified under a distinct discipline called HIV fusion inhibitors. Resistance to HIV fusion inhibitors and their solutions have also been discussed in this review. Copyright

Cdc42: Role in Cancer Management

Contribution of Cdc42, a member of Rho family, has been characterized for the beginning of variety of cellular responses including cellular transformation, cell division, cell invasion, migration, invadopodia formation, enzyme activity, filopodia formation, and cell polarity in cells. Deregulation of Cdc42 can alter the normal functioning of the cells, responsible for the initiation of signaling pathways and is correlated with several pathogenic processes such as cancer. Therefore, maintaining the level of Cdc42 and its effectors in cells, tumor progression can be controlled. Therefore, it can be suggested that deeper understanding about the Cdc42 contribution in cancer cell progression at molecular level can approach to the development of Cdc42 inhibitors in cancer management.

Role of Interleukin-6 in Development of Insulin Resistance and Type 2 Diabetes Mellitus

Interleukin-6 (IL-6) is a proinflammatory cytokine that decisively induces the development of insulin resistance and pathogenesis of type 2 diabetes mellitus (T2DM) through the generation of inflammation by controlling differentiation, migration, proliferation, and cell apoptosis. The presence of IL-6 in tissues is a normal consequence, but its irregular production and long-term exposure leads to the development of inflammation, which induces insulin resistance and overt T2DM. There is a mechanistic relationship between the stimulation of IL-6 and insulin resistance. IL-6 causes insulin resistance by impairing the phosphorylation of insulin receptor and insulin receptor substrate-1 by inducing the expression of SOCS-3, a potential inhibitor of insulin signaling. In this article, we have briefly described how IL-6 induces the insulin resistance and pathogenesis of T2DM. The prevention of inflammatory disorders by blocking IL-6 and IL-6 signaling may be an effective strategy for the treatment of insulin resistance and T2DM.

Analgesic, anti-inflammatory and anti-pyretic activities of Caesalpinia decapetala

Introduction: In many pathological conditions, pain, inflammation and fever are interdependent to each other. Due to the use of synthetic drugs, many unwanted effects usually appear. Various studies have been conducted on Caesalpinia decapetala (C. decapetala) to evaluate its effects in the treatment of various diseases but no sufficient scientific literature is available online to prove its analgesic, anti-inflammatory and anti-pyretic activities. Methods: The analgesic, anti-inflammatory and anti-pyretic activities of 70% aqueous methanolic and n-hexane extracts of C. decapetala was evaluated using Swiss albino mice (20-30 g). Results: The results showed that aqueous methanolic extract of C. decapetala at the dose of 100 mg/kg exhibited significant (p< 0.05) activities in various pain models including acetic acid-induced writhing (18.4 ± 0.53), formalin-induced licking (275 ± 4.18) and hot plate method (2.3 ± 0.0328); whereas, n-hexane extract showed its effects in acetic acid-induced writhing (20 ± 0.31), formalin-induced licking (293 ± 1.20) and hot plate method (2.224 ± 0.029) compared to the effects observed in control group animals. Similarly, the aqueous methanolic extract of C. decapetala after 2 h of treatment exhibited more significant anti-inflammatory (0.66 ± 0.06) and anti-pyretic (38.81 ± 0.05) activities compared to the control group animals. Conclusion: From the findings of our present study, we concluded that the aqueous methanolic extract of C. decapetala has stronger analgesic, anti-inflammatory and anti-pyretic effects than its n-hexane extract. Further studies are required to investigate the active constituents of C. decapetala that exhibit analgesic, anti-inflammatory and anti-pyretic activities.

SUSTAINED RELEASE HYDROPHILIC MATRICES BASED ON XANTHAN GUM AND HYDROXYPROPYL METHYLCELLULOSE: DEVELOPMENT, OPTIMIZATION, IN VITRO AND IN VIVO EVALUATION

Hydrophilic matrices of xanthan gum and hydroxypropyl methylcellulose were prepared by direct compression using diclofenac sodium as model drug. All formulations were subjected to physical tests, FTIR studies and dissolution studies at pH 1.2 and 6.8, to evaluate drug release kinetics. In vivo studies were carried out in rabbits using single latin cross over design and pharmacokinetic parameters were analyzed by using one way ANOVA and LSD. Physical parameters of all formulations were within limits with stability of drug during direct compression and absence of drug polymer interaction as evident by FTIR spectra. In vitro release studies showed that both polymers were able to retard the drug release but matrices containing XG showed initial greater burst release in acidic media (pH 1.2) which was absent in HPMC matrices due to delayed hydration and pH independent gelling mechanism in HPMC. XG matrices showed greater sustained release pattern in phosphate buffer solution (pH 6.8) over twenty-four hours of study due to formation of gel and viscous solution around matrices. All the formulation followed Higuchi kinetics and Korsmeyer-Peppas equation confirms the involvement of multiple drug release mechanisms release from hydrophilic matrices. Plasma drug concentration in rabbits after oral administration was used to calculate different pharmacokinetic parameters, which showed the inverse relationship of the AUC, AUMC and Cmax of the drug with polymer concentrations. Statistical evaluation confirms the role of polymer concentration on delayed release. XG matrices demonstrated fewer time to reach Tmax, higher Cmax and AUC0-∞ values as compared to batches formulated with HPMC, owing to burst release of drug from XG matrices in acidic media. Both formulations showed poor IVIVC due to in vitro and in vivo difference of pH and ionic strength.

First chikungunya outbreak in Pakistan: a trail of viral attacks

Despite explicit warning from the National Institute of Health, Pakistan experienced its first chikungunya outbreak in the metropolis of Karachi. We underscore the attention of health authorities and healthcare professionals towards contributing factors associated with this outbreak and the measures required to combat this viral disease.