Antihyperglycemic and Antihyperlipidemic Evaluation of Zingiber officinale,Anethum graveolens and Citrullus colocynthis Extracts with Different Polarities in Streptozotocin-Induced Diabetic Rats

Pharmaceutical Chemistry Journal - Zingiber officinale (ginger, II), Citrullus colocynthis (CC, III) and Anethum graveolens (dill, IV) are functional medicinal plants containing beneficial...     

Combined atorvastatin and pentoxifylline in ameliorating inflammation induced by complete Freund’s adjuvant

Inflammopharmacology - Injection of complete Freund’s adjuvant (CFA) into one of the footpads of Wistar rats promotes swelling in all the footpads (including non-injected footpads) in the...     

Lithium attenuates pain-related behavior in a rat model of neuropathic pain: possible involvement of opioid system

Lithium is a major drug for bipolar disorder and mania. Recently, many studies have shown the neuroprotective effect of lithium in different models of neurodegenerative diseases. The present study was carried out to examine the effect of lithium in a rat model of neuropathic pain induced by partial sciatic nerve ligation and the possible role of opioid system in this effect. To do so, animals received acute injection of saline, lithium (5, 10 and 15 mg/kg,) and naloxone (1 mg/kg) or the combination of naloxone (1 mg/kg) with lithium (10 mg/kg) intraperitoneally on the testing days. Thermal hyperalgesia, mechanical and cold allodynia were measured on the days 3, 5, 7, 10 and 14 after surgery. Lithium decreased thermal hyperalgesia scores with dose of 5, 10 and 15 mg/kg and cold and mechanical allodynia scores with dose of 10 and 15 mg/kg, significantly. The opioid antagonist naloxone prevented the effect of lithium on thermal hyperalgesia and mechanical allodynia while it did not show any effect on the acetone-induced cold allodynia. Our results suggest that lithium can be considered as a therapeutic potential for the treatment of some aspects of neuropathic pain and that the opioid system may be involved in the lithium-induced attenuation of thermal hyperalgesia and mechanical allodynia.     

Azidothymidine hinders arsenic trioxide-induced apoptosis in acute promyelocytic leukemia cells by induction of p21 and attenuation of G2/M arrest

To enhance anticancer efficacy of the arsenic trioxide (ATO), the combination of ATO and azidothymidine (AZT), with convergence anti-telomerase activity, were examined on acute promyelocytic leukemia (APL) cell line, NB4. In spite of an induction of apoptosis by both drugs separately and a synergistic effect of them on hTERT down-regulation and telomerase inhibition, the ATO-induced cytotoxicity was reduced when it was used in combination with AZT. AZT attenuated the ATO effects on viability, metabolic activity, DNA synthesis, and apoptosis. These observations, despite the deflection from the main goal of this study, dedicate an especial opportunity to elucidate the importance of some of the mechanisms that have been suggested by which ATO induces apoptosis. Cell cycle distribution, ROS level, and caspase-3 activation analyses suggest that AZT reduced the ATO-induced cytotoxic effect possibly via relative induction and diminution of cells accumulated in (G1, S) and (G2/M) phase, respectively, as well as through attenuation of ROS generation and subsequent caspase-3 inhibition. QRT-PCR assay revealed that induction of p21expression by the combined AZT/ATO compared to ATO alone could be a reason for the relative decline of cells accumulation in G2/M and the increase of cells in G1 and S phases. Therefore, the G2/M arrest and ROS generation are likely principle mediators for the ATO-induced apoptosis and can be used as a guide to design rational combinatorial strategies involving ATO and agents with G2/M arrest or ROS generation capacity to intensify ATO-induced apoptosis.     

Bilateral basal ganglia involvement in a patient with Griscelli syndrome.

We report a 6-year-old Iranian boy with silvery-gray hair, eyelashes and the eyebrows who was admitted because of seizures and subsequent stupor. He had previous history of acute hemiparesis at 1 year of age and hepatitis-like syndrome 3 months ago. Microscopic examination of the patient's hair shaft revealed different sized clumps of melanin seen in the center of the shafts. Bone marrow aspiration revealed erythroid hyperplasia and erythrophagocytic cells. Bilateral frontal cortical and subcortical high signal lesions, dirty white matter, high signal areas in the upper pons and in both caudates and lentiform nuclei in T2 WI were the brain MRI findings of the patient. He died in the accelerated phase of Griscelli Syndrome (GS) type 2. To our knowledge we report the first case of GS from Iran.     

Preparation,characterization, and cytotoxic effects of liposomal nanoparticles containing cisplatin: an in vitro study

Cisplatin is a chemotherapeutic agent used for treating various malignancies. The study aimed to prepare pegylated liposomal cisplatin and evaluate its efficacy against human breast cancer cell line MCF‐7. Drug‐loaded nanoparticles were synthesized by reverse phase evaporation technique. The study is highlighted by extensive characterization of nanoparticles in terms of nanoparticle morphology, type of drug entrapment, cisplatin retention capability, and cytotoxicity effects. The size, size distribution, and zeta potential of nanodrug were estimated 142 nm, 0.33, and ?22 mV, respectively. Drug‐loading efficiency was equal to 48% that occurred physically. Furthermore, high retention capability (39% of drug was released after 72 h) with significantly enhanced cytotoxicity of nanodrug (1.75 times more than the standard drug) confirmed the potency of liposomal nanoparticles as proper cisplatin carrier.     

Duchenne muscular dystrophy: an updated review of common available therapies

Background and purpose: Duchenne muscular dystrophy (DMD) is a lethal progressive pediatric muscle disorder and genetically inherited as an X-linked disease that caused by mutations in the dystrophin gene. DMD leads to progressive muscle weakness, degeneration, and wasting; finally, follows with the premature demise in affected individuals due to respiratory and/or cardiac failure typically by age of 30. For decades, scientists tried massively to find an effective therapy method, but there is no absolute cure currently for patients with DMD, nevertheless, recent advanced progressions on the treatment of DMD will be hopeful in the future. Several promising gene therapies are currently under investigation. These include gene replacement, exon skipping, suppression of stop codons. More recently, a promising gene editing tool referred to as CRISPR/Cas9 offers exciting perspectives for restoring dystrophin expression in patients with DMD. This review intents to briefly describe these methods and comment on their advances. Since DMD is a genetic disorder, it should be treated by replacing the deficient DMD copy with a functional one. However, there are different types of mutations in this gene, so such therapeutic approaches are highly mutation specific and thus are personalized. Therefore, DMD has arisen as a model of genetic disorder for understanding and overcoming of the challenges of developing personalized genetic medicines, consequently, the lessons learned from these approaches will be applicable to many other disorders.

Conclusions: This review provides an update on the recent gene therapies for DMD that aim to compensate for dystrophin deficiency and the related clinical trials.     

A comparison between on-demand usage of rFVIIa vs prophylaxis use of emicizumab in high titer inhibitory hemophilia A patients in Iran: A cost–utility analysis

Background:Hemophilia A (HA) is an inherited X-linked bleeding disease with costly treatment, especially for high titer inhibitory patients. Emicizumab, a new humanized bispecific antibody, has been approved for use to prevent or reduce the frequency of bleeding episodes in HA patients with inhibitors. This study evaluated the cost-utility of emicizumab prophylaxis (EP) in comparison with recombinant factor VII activated on-demand treatment in HA patients with inhibitors.Methods:A life-time Markov model with payer and societal perspectives was developed in different age groups with different annual bleeding rates (ABR). Efficacy of treatments were extracted from HAVEN trials. Utilities were retrieved from published evidence. Costs were calculated based on Iran food and drug administration official website, national tariff book for medical services and hospital data. One-way deterministic sensitivity analysis was performed.Results:EP was dominant choice in comparison with on-demand administration of recombinant factor VII activated in all age groups with ABR 20 and 25, and it remained dominant in patients with age 2 and age 12 at start point with ABR 16 and 17. The reported incremental cost-effectiveness ratio for the group with ABR 18 at the age 20, was 12,936 United States Dollars which is lower than the acceptable threshold of cost-effectiveness in Iran (1–3 gross domestic product per capita) and EP can be considered as cost-effective choice in this scenario.Conclusion:EP was found to be a dominant and cost-effective choice for Iranian HA patients with factor VIII inhibitors with ABR 18 and above with considerable cost saving.