Pyridine: the scaffolds with significant clinical diversity

The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research. This privileged scaffold has been consistently incorporated in a diverse range of drug candidates approved by the FDA (Food and Drug Administration). This moiety has attracted increasing attention from several disease states owing to its ease of parallelization and testing potential pertaining to the chemical space. In the next few years, a larger share of novel pyridine-based drug candidates is expected. This review unifies the current advances in novel pyridine-based molecular frameworks and their unique clinical relevance as reported over the last two decades. It highlights an inclination to the use of pyridine-based molecules in drug crafting and the subsequent emergence of several potent and eligible candidates against a range of diversified diseases.

The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research.     

Present and future fertility preservation strategies for female cancer patients

As survival rates with cancer treatment are steadily increasing, many women are now facing sterility due to treatment induced ovarian failure. This review will attempt to summarize the options for trying to preserve fertility in these patients. The optimal approach depends on the type of cancer, the type of treatment (e.g., radiation and/or chemotherapy), time available till onset of treatment, patient's age, and whether the patient has a partner. Ovarian transposition remains the standard of care for women undergoing pelvic radiation, although it has been suggested that it may be combined with ovarian tissue cryopreservation. For patients about to receive chemotherapy or whole body radiation, in vitro fertilization (IVF) with embryo cryopreservation is a well established treatment with a good success rate. However, it requires delaying cancer treatment for 2 to 4 weeks and a partner or willingness to use donor sperm. When these criteria cannot be met, more experimental options include oocyte cryopreservation for later IVF and ovarian tissue cryopreservation. The tissue may be autotransplanted back to the pelvis, when the patient is in remission, to attempt spontaneous conception or subcutaneously for easy access of follicle aspiration for IVF. Alternatively, it may be xenografted to immunocompromised mice to induce follicle maturation in preparation for retrieval for IVF. Emerging treatment options for fertility preservation include medication to prevent chemotherapy-induced oocyte damage and oocyte construction from somatic cell nuclei. IVF with donor oocyte remains an established option with a very high success rate for those who fail to conceive with the above measures or who elect not to avail themselves to experimental procedures. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to demonstrate knowledge about fertility preservation when counseling appropriate female cancer patients, recall current clinical strategies to assist women cancer patients to try to maintain their fertility if they wish, and appraise future strategies as they develop.     

Protective effects of Terminalia arjuna against Doxorubicin-induced cardiotoxicity

Terminalia arjuna has been marked as a potential cardioprotective agent since vedic period. The present study was aimed to investigate the effects of butanolic fraction of Terminalia arjuna bark (TA-05) on Doxorubicin (Dox)-induced cardiotoxicity. Male wistar rats were used as in vivo model for the study. TA-05 was administered orally to Wistar rats at different doses (0.42 mg/kg, 0.85 mg/kg, 1.7 mg/kg, 3.4 mg/kg and 6.8 mg/kg) for 6 days/week for 4 weeks. Thereafter, all the animals except saline and TA-05-treated controls were administered 20 mg/kg Dox intraperitonially. There was a significant decrease in myocardial superoxide dismutase (38.94%) and reduced glutathione (23.84%) in animals treated with Dox. Concurrently marked increase in serum creatine kinase-MB (CKMB) activity (48.11%) as well as increase in extent of lipid peroxidation (2.55-fold) was reported. Co-treatment of TA-05 and Dox resulted in an increase in the cardiac antioxidant enzymes, decrease in serum CKMB levels and reduction in lipid peroxidation as compared to Dox-treated animals. Electron microscopic studies in Dox-treated animals revealed mitochondrial swelling, Z-band disarray, focal dilatation of smooth endoplasmic reticulum (SER) and lipid inclusions, whereas the concurrent administration of TA-05 led to a lesser degree of Dox-induced histological alterations. These findings suggest that butanolic fraction of Terminalia arjuna bark has protective effects against Dox-induced cardiotoxicity and may have potential as a cardioprotective agent.     

Cell phones and male infertility: dissecting the relationship

There has been a tremendous increase in the use of mobile phones in the past decade and concerns are growing about the possible hazardous effects of radio-frequency electromagnetic waves (EMW) emitted by these devices on human health. Preliminary studies, though with limitations in study design, suggest a possible link between cell phone use and infertility. A recent study found that use of cell phones adversely affects the quality of semen by decreasing the sperm counts, motility, viability and morphology. Evidence of detrimental effect of mobile phones on male fertility is still equivocal as studies have revealed a wide spectrum of possible effects ranging from insignificant effects to variable degrees of testicular damage. Although previous studies suggested a role of cell phone use in male infertility, the mode of action of EMW emitted from cell phones on the male reproductive system is still unclear. EMW can affect the reproductive system via an EMW-specific effect, thermal molecular effect or combination of both. Studies performed on human males are scarce and therefore further studies with a careful design are needed to determine the effect of cell phone use on male-fertilizing potential.     

Time after excision and temperature alter ex vivo tissue relaxation time measurements

Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40°C, at room temperature (28°C), or in an ice bath (4°C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40°C (20-MHz spectrometer), the T1 of liver decreased from 280 msec ± 8 to 212 msec ± 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec ± 3 to 208 msec ± 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors.