Clinical aspects of 49 infertile males with 45,X/46,XY mosaicism karyotype: A case series

Disorders of sex development (DSD) are congenital abnormalities as an atypical development process in either gonadal or chromosomal structure. It is the cause of the abnormality in phenotype and characteristics. Chromosomal analysis plays an important role in the DSD determination. 45,X/46,XY mosaicism is a rare karyotype, and its prevalence is about 1.5 in 10,000 newborns. It affects the growth, hormonal balance, gonad development and histology. All data such as height, male general appearance, testis size and volume, external genitalia, spermogram and hormonal levels, testis pathology, Y chromosome microdeletion and karyotype, and assisted reproductive technology (ART) outcome were recorded based on patients profile and history. We investigated 64 infertile males with 45,X/46,XY mosaicism. Fifteen cases who had structural abnormalities in Y chromosome were excluded. From 49 available spermogram, 21 cases reported as azoospermic men, while 28 of them classified as nonazoospermic patients in which four of them displayed normal spermogram. According to hormonal evaluation, there were no significant differences between azoospermic and nonazoospermic groups. In azoospermia, only three couples underwent an ART cycle in which all of them failed. From 14 nonazoospermic cases who entered into the ART cycle, three cases experienced a successful pregnancy that one of the prosperous outcomes was twins. In 45,X/46,XY cases, both 45,X and 46,XY cell lines are seen. Various distributions of both cell lines can reflect a wide range of phenotypes that may be the most comprehensive evaluation in infertile males with 45,X/46,XY karyotype. It assumes that karyotyping as a main diagnostic test can enable us to find these rare cases.     

Collins’ sign: validation of a clinical sign in cholelithiasis

Background  

Cholelithiasis typically presents with right upper quadrant pain, as can pain from other right upper quadrant organs. Pain of cholelithiasis is often referred to tip of scapula. Professor Paddy Collins drew attention to fact that patients with gallstone pain would attempt to demonstrate this by placing their hand behind the back and thumb pointing upwards. This became known amongst his students as Collins’ sign.     

Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia may explain medicinal use of turmeric in Alzheimer's disease

Curcuminoids (a mixture of curcumin, bisdemethoxycurcumin and demethoxycurcumin) share vital pharmacological properties possessed by turmeric, a well known curry spice, considered useful in Alzheimer's disease (AD). The aim of this study was to evaluate if curcuminoids possess acetylcholinesterase (AChE) inhibitory and memory enhancing activities. The in-vitro and ex-vivo models of AChE inhibitory activity were used along with Morris water maze test to study the effect on memory in rats. Curcuminoids inhibited AChE in the in-vitro assay with IC₅₀ value of 19.67, bisdemethoxycurcumin 16.84, demethoxycurcumin 33.14 and curcumin 67.69 µM. In the ex-vivo AChE assay, curcuminoids and its individual components except curcumin showed dose-dependent (3-10 mg/kg) inhibition in frontal cortex and hippocampus. When studied for their effect on memory at a fixed dose (10 mg/kg), all compounds showed significant (p < 0.001) and comparable effect in scopolamine-induced amnesia. These data indicate that curcuminoids and all individual components except curcumin possess pronounced AChE inhibitory activity. Curcumin was relatively weak in the in-vitro assay and without effect in the ex-vivo AChE model, while equally effective in memory enhancing effect, suggestive of additional mechanism(s) involved. Thus curcuminoids mixture might possess better therapeutic profile than curcumin for its medicinal use in AD.     

A novel approach to prepare insulin-loaded poly(lactic-co-glycolic acid) microcapsules and the protein stability study

The purpose of this study was to propose a new preparation method to fabricate insulin-loaded poly(lactic-coglycolic acid) (PLGA) microparticles satisfying protein loading, release profiles, burst release, and particularly stability of the encapsulated protein. Insulin-loaded microcapsules were produced by a single phase o/o solvent evaporation method. The characteristics of the microcapsules were determined by various methods: the surface morphology and size of microparticles by atomic force microscopy and scanning electron microscopy, insulin crystalinity and drug-polymer interactions by XRD, DSC, and FTIR, chemical integrity and aggregation of insulin using HPLC and SDS-PAGE, the protein secondary structure by far ultraviolet-circular dichroism (CD), the antigenicity activity of insulin with ELISA techniques. PLGA microparticles showed smooth surfaces with microcapsule. Encapsulation efficiency of 51% and constant insulin release rate with initial insulin burst release of 24% was obtained. Encapsulated and released insulin was in the intact form and it was dispersed in crystalline state in the polymer matrix. Ease of manufacturing under mild preparation conditions, high level of drug entrapment, desirable release pattern with relatively low initial burst effect and an ability to preserve protein structure are the advantages which are offered by the developed protein encapsulation method.     

Blood pressure lowering,cardiovascular inhibitory and bronchodilatory actions of Achillea millefolium

Achillea millefolium Linn. (Asteraceae) is used in folk medicine for the treatment of overactive cardiovascular and respiratory ailments. This study describes its hypotensive, cardio‐depressant, vasodilatory and bronchodilatory activities. The crude extract of Achillea millefolium (Am.Cr) caused a dose‐dependent (1–100 mg/kg) fall in arterial blood pressure of rats under anaesthesia. In spontaneously beating guinea‐pig atrial tissues, Am.Cr exhibited negative inotropic and chronotropic effects. In isolated rabbit aortic rings, Am.Cr at 0.3–10 mg/mL relaxed phenylephrine (PE, 1 µm ) and high K⁺ (80 mm )‐induced contractions, as well as suppressed the PE (1 µm ) control peaks obtained in Ca⁺⁺‐free medium, like that caused by verapamil. The vasodilator effect of Am.Cr was partially blocked by N_ω‐nitro‐l ‐arginine methyl ester in endothelium intact preparations. In guinea‐pig tracheal strips, Am.Cr inhibited carbachol (CCh, 1 µm ) and K⁺‐induced contractions. These results indicate that Achillea millefolium exhibits hypotensive, cardiovascular inhibitory and bronchodilatory effects, thus explaining its medicinal use in hyperactive cardiovascular and airway disorders, such as hypertension and asthma. Copyright © 2010 John Wiley & Sons, Ltd.     

Particle size design of PLGA microspheres for potential pulmonary drug delivery using response surface methodology

The large surface area, good vascularization, immense capacity for solute exchange and ultra-thinness of the alveolar epithelium are unique features of the lung facilitating systemic drug delivery via pulmonary administration. The efficacy and safety of many new and existing inhaled therapies may be enhanced through advanced controlled-release systems by using polymer particles. Poly (D,L-lactic-co-glycolic acid) (PLGA) is well known by its safety in biomedical preparations which has been approved for human use by the FDA. The optimum aerodynamic particle size distribution for most inhalation aerosols has generally been recognized to be in the range of 1-5 microns. PLGA microspheres, therefore, were prepared by a developed oil-in-oil solvent evaporation method and characterized. A four-factor, three levels Box-Behnken design was used for the optimization procedure with temperature, stirring speed, PLGA and surfactant concentration as independent variables. Particle size and polydispersity of microspheres were considered as dependent variables. PLGA microparticles were prepared successfully in desired size for pulmonary delivery by solvent evaporation method. It was found that the particle size of microspheres could be easily controlled. It was also proved that response surface methodology could efficiently be applied for size characterization and optimization of PLGA microparticles for pulmonary drug delivery.     

Pharmacological basis for the use of Borago officinalis in gastrointestinal, respiratory and cardiovascular disorders

AIM OF THE STUDY: In this study, we investigated the crude extract of Borago officinalis leaves (Bo.Cr) for its antispasmodic, bronchodilator, vasodilator and cardio-depressant activities to rationalize some of the traditional uses. MATERIALS AND METHODS: Bo.Cr was studied using different isolated tissue preparations including rabbit jejunum, trachea, aorta, and guinea-pig atria. RESULTS: Bo.Cr which was tested positive for flavonoids, coumarins, sterols and tannins produced a concentration-dependent relaxation of spontaneous and K+ (80mM)-induced contractions in isolated rabbit jejunum preparations, suggestive of Ca++ antagonist effect, which was confirmed when pretreatment of the tissue with Bo.Cr produced a rightward shift in the Ca++ concentration-response curves like that caused by verapamil. In rabbit tracheal preparations, Bo.Cr relaxed the carbachol (1microM) and K+-induced contractions. Verapamil also produced non-specific inhibitory effect. In rabbit aorta preparations, Bo.Cr exhibited vasodilator effect against phenylephrine and K+-induced contractions similar to verapamil. When tested in guinea-pig atria, Bo.Cr caused inhibition of both atrial force and rate of contractions. CONCLUSIONS: These results suggest that the spasmolytic effects of Bo.Cr are mediated possibly through Ca++ antagonist mechanism, which might explain the traditional use of Borago officinalis in hyperactive gastrointestinal, respiratory and cardiovascular disorders.     

Phytochemical, pharmacological and ethnobotanical studies of Rhazya stricta Decne

Rhazya stricta Decne. is an important medicinal species that is rich in alkaloids containing anticancer alkaloids also. This paper reviews phytochemical, pharmacological and ethnobotanical studies of R. stricta. Phytochemical and pharmacological aspects of the species have been thoroughly explored. Over 100 alkaloids have been isolated from R. stricta, but the pharmacological activities are known for only a few of these compounds. Very few ethnobotanical studies of R. stricta have been done, and there is a particular need for such studies in various regions of South Asia and in Middle Eastern countries where the species grows. These ethnobotanical studies should investigate herbal recipes of R. stricta and their use for curing diseases. The genetic diversity, chemotaxonomy and allelopathy of R. stricta have not yet been explored, and these studies are recommended, with the ultimate goal of benefiting local communities in regions where R. stricta grows. This should be achieved by sharing knowledge and through the manufacture of herbal drugs from R. stricta's active chemical constituents, while protecting intellectual property rights and following the World Health Organization's guidelines for safety and efficacy.