Antiplatelet properties of snake venoms: a mini review

Abstract

Snake venoms contain various active compounds including pharmacological polypeptides and proteins with various molecular weights. Some of these polypeptides and proteins are enzymatic or act as proteinases and hugely impact thrombosis and hemostasis in other species including humans. Numerous active molecules with enzymatic and non-enzymatic functions in snake venoms have been identified so far. For example, phospholipase A₂ enzymes, l-amino acid oxidases, metalloproteinases, serine proteinase, disintegrins, and C-type lectin-like proteins are the main molecules. They have pro- or anti-thrombotic effects depending on various variables and may stimulate or inhibit platelet aggregation. In the present updated article, we reviewed the effects of snake venoms on platelets, and the underlying mechanisms of action will be discussed in detail.     

The epigenetic alterations of human sperm cells caused by heroin use disorder

The molecular mechanisms of drug use on sexual health are largely unknown. We investigated, the relationship between heroin use disorder and epigenetic factors influencing histone acetylation in sperm cells. The volunteers included twenty-four 20- to 50-year-old men with a normal spermogram who did not consume any drugs and twenty-four age- to BMI-matched men who consume only the drug heroin for more than last four months. HDAC1 and HDAC11 mRNA expression levels in spermatozoa and miR-34c-5p and miR-125b-5p expression levels in seminal plasma were measured. The heroin-user group showed significantly increased white blood cell counts and decreased sperm motility and survival rates (8.61 ± 1.73, 21.50 ± 3.11, 69.90 ± 4.69 respectively) as compared to the control group (1.49 ± 0.32, 38.82 ± 3.05, 87.50 ± 0.99 respectively) (p ≤ .001). An increase in DNA fragmentation index (DFI) (heroin-user group: 41.93 ± 6.59% and control group: 10.14 ± 1.43%, p = .003), a change in frequency of HDAC1 (heroin-user group: 1.69 ± 0.55 and control group: 0.45 ± 0.14, p = .045) and HDAC11 (heroin-user group: 0.29 ± 0.13 and control group: 2.36 ± 0.76, p = .019) in spermatozoa and a significant decrease in seminal miR-125b-5p abundance (heroin-user group: 0.37 ± 0.11 and control group: 1.59 ± 0.47, p = .028) were reported in heroin consumers. Heroin use can lead to male infertility by causing leukocytospermia, asthenozoospermia, DFI elevation in sperm cells and alterations in seminal RNA profile.     

Chitosan-Raloxifene nanoparticle containing doxorubicin as a new double-effect targeting vehicle for breast cancer therapy

Backgroundtreatment of breast cancer as one of the most common cancers in the world remains an important area of drug development based on nanoparticulate systems. Effective targeted therapy of affected cells based on ligand conjugate biocompatible polymeric nanoparticles is an attractive perspective in this context.ObjectiveIn this study, a novel double effect nanoparticle based on Chitosan-Raloxifene conjugate was prepared for adjuvant therapy (hormone and chemo therapy) and drug targeting to breast cancer cells via estrogen receptor (ER).MethodsChitosan-raloxifene conjugate was synthesized. Related nanoparticles containing doxorubicin (DOX) were prepared and characterized. Experimental design study was performed to determine the optimum levels of variables in the preparation of nanoparticle. Drug loading, release, nanoparticle stability, and the effect of nanoparticles on cell viability were evaluated. Further, inhibition tests were performed to demonstrate that the function of these novel nanoparticles is mediated via ER.ResultsChitosan-raloxifene conjugate was successfully synthesized. The prepared nanoparticles showed sizes within 25–35 nm, more than 95% drug loading, about 60% of drug release and desired stability after 24 h. XTT assay on MCF-7 cell line illustrated that these nanoparticles could inhibit the cellular growth up to 60%. The results from inhibition tests revealed that prepared nanoparticles can inhibit cell growth via ER blocking.ConclusionThis study introduced chitosan-raloxifene nanoparticles containing doxorubicin as a novel targeting agent for adjuvant therapy of breast cancer. Open in a separate windowGraphical abstractElectronic supplementary materialThe online version of this article (10.1007/s40199-020-00338-9) contains supplementary material, which is available to authorized users.     

Association of HTR1A gene polymorphisms with obsessive–compulsive disorder and its treatment response: the influence of sex and clinical characteristics

Objective: There have been controversial results in the literature on the association between HTR1A polymorphisms (rs10042486, C-1019G, and Gly272Asp) and obsessive–compulsive disorder (OCD). Here, the plausibility for such genetic and pharmacogenetic association was investigated by assessing a sample of Iranian OCD patients.

Method: OCD patients had fulfilled the criteria for DSM-IV-TR with Y-BOCS scores higher than 9. A total of 207 controls and 205 patients’ blood samples were genotyped by means of PCR-RFLP.

Results: The results showed that there was no association between these three SNPs and the treatment response. The distribution of rs10042486 genotypes was significantly different in the patients compared to the controls. The association analyses of the C-1019G showed significant differences in the genotypic frequency of the patients with or without a positive family history of psychiatric disorders. Similar differences in female patients were also observed. We found that the age of onset also associates with the C-1019G polymorphism but only in the female patients. No association of Gly272Asp polymorphism and OCD was observed in this study.

Conclusion: We concluded that among the HTR1A polymorphisms, only the association of rs10042486 CT genotype and OCD was statistically significant. The association of C-1019G with OCD by considering the age of onset and family history was just significant in the female patients. No significant association between the studied HTR1A SNPs with treatment response was observed. Acquiring both positive and negative pharmacogenetic outcomes in each population helps to select the appropriate medication for a particular patient with fewer side effects.     

Innovative procedure in surgical management of chronic lymphoedema

Background: Lymphoedema is the result of impaired lymphatic drainage from the affected organ. This abnormality can be primary or secondary. Different non‐operative and operative approaches have been introduced to treat chronic lymphoedema. In the present study, we describe a new surgical technique and compare its results with other more commonplace methods. Materials and Methods: The study included 296 patients who had been diagnosed with chronic lower extremity lymphoedema and who had not responded to non‐operative management for at least 6 months. Data was collected over 15 years, between March 1987 and March 2002. Doppler ultrasonography of the deep venous system was routinely undertaken in all patients to confirm its patency. The 296 patients underwent surgery and their progress was followed for at least 1 year postoperatively. Results: All of the patients were operated on using our new technique, which is a modified form of the Homan techniques. The outcome was excellent, and 89.2% of patients were free of complication. The most common complication was wound seroma. Conclusions: Considering the difficulties associated with the treatment of chronic lymphoedema and the variety of surgical options, our method achieves excellent results, and could even become the standard operative procedure for treating intractable forms of disease.