In vivo cardioprotection by pitavastatin from ischemic-reperfusion injury through suppression of IKK/NF-κB and upregulation of pAkt-e-NOS

Recent studies have uncovered the beneficial effects of statin in cardiovascular diseases; however, the role of pitavastatin in ischemia-reperfusion (IR)-induced apoptosis and myocardial damage is not established. Therefore, in this study, we aim to investigate whether pitavastatin treatment attenuates myocardial IR injury via regulating oxidative stress, inflammation, apoptosis, and phosphorylated protein kinase B (pAkt) endothelial nitric oxide synthase (e-NOS) pathways. After the 14-day treatment with pitavastatin (0.16-0.64 mg·kg·d, po) or saline, rats were subjected to 45 minutes of ischemia by occluding the left anterior descending coronary artery and to 60 minutes of reperfusion to induce myocardial damage. Pitavastatin at a dose of 0.32 and 0.64 mg/kg significantly improved cardiac function as evidenced by the normalization of the mean arterial pressure, heart rate, ±LVdP/dtmax, and left ventricular end-diastolic pressure as compared with the IR control. Additionally, pitavastatin dose-dependently normalized myocardial antioxidants, lactate dehydrogenase, and thiobarbituric acid reactive substances along with decreased serum tumor necrosis factor-α level and creatine kinase isoenzyme-MB activity. Furthermore, pitavastatin enhanced pAkt, (p) e-NOS, Bcl-2, and suppressed IκB kinase/nuclear factor-kappa B, nitrotyrosine (NO inactivation product), Bax, and capases-3 protein expression in the heart. Morphological assessments of the IR-challenged myocardium showed that 0.32 and 0.64 mg/kg of pitavastatin decrease myocardial necrosis and inflammatory changes. Thus, pitavastatin reduced IR-induced infarction and dysfunction via the augmentation of endogenous antioxidant, suppression of IκB kinase/nuclear factor-kappa B, activation of pAkt-e-NOS, and/or decreased NO inactivation and apoptosis.     

Dopamine: the forgotten felon in type 2 diabetes

This paper reviews recent patents and development related to bromocriptine and other dopaminergic agents, being used or suggested for use in the management of diabetes. The article discusses the contribution of dopaminergic pathways to glucose, energy and weight homeostasis. The mechanism of action of bromocriptine, its pharmacological properties, efficacy, safety and tolerability are assessed. The article also covers recent patents which may be utilized to improve the efficiency and tolerability of dopamine-based therapy in diabetes mellitus.     

Myelopotentiating effect of curcumin in tumor-bearing host: role of bone marrow resident macrophages

The present investigation was undertaken to study if curcumin, which is recognized for its potential as an antineoplastic and immunopotentiating agent, can also influence the process of myelopoiesis in a tumor-bearing host. Administration of curcumin to tumor-bearing host augmented count of bone marrow cell (BMC) accompanied by an up-regulated BMC survival and a declined induction of apoptosis. Curcumin administration modulated expression of cell survival regulatory molecules: Bcl2, p53, caspase-activated DNase (CAD) and p53-upregulated modulator of apoptosis (PUMA) along with enhanced expression of genes of receptors for M-CSF and GM-CSF in BMC. The BMC harvested from curcumin-administered hosts showed an up-regulated colony forming ability with predominant differentiation into bone marrow-derived macrophages (BMDM), responsive for activation to tumoricidal state. The number of F4/80 positive bone marrow resident macrophages (BMM), showing an augmented expression of M-CSF, was also augmented in the bone marrow of curcumin-administered host. In vitro reconstitution experiments indicated that only BMM of curcumin-administered hosts, but not in vitro curcumin-exposed BMM, augmented BMC survival. It suggests that curcumin-dependent modulation of BMM is of indirect nature. Such prosurvival action of curcumin is associated with altered T_H1/T_H2 cytokine balance in serum. Augmented level of serum-borne IFN-γ was found to mediate modulation of BMM to produce enhanced amount of monokines (IL-1, IL-6, TNF-α), which are suggested to augment the BMC survival. Taken together the present investigation indicates that curcumin can potentiate myelopoiesis in a tumor-bearing host, which may have implications in its therapeutic utility.     

Uracil excision repair in Mycobacterium tuberculosis cell-free extracts

Uracil excision repair is ubiquitous in all domains of life and initiated by uracil DNA glycosylases (UDGs) which excise the promutagenic base, uracil, from DNA to leave behind an abasic site (AP-site). Repair of the resulting AP-sites requires an AP-endonuclease, a DNA polymerase, and a DNA ligase whose combined activities result in either short-patch or long-patch repair. Mycobacterium tuberculosis, the causative agent of tuberculosis, has an increased risk of accumulating uracils because of its G + C-rich genome, and its niche inside host macrophages where it is exposed to reactive nitrogen and oxygen species, two major causes of cytosine deamination (to uracil) in DNA. In vitro assays to study DNA repair in this important human pathogen are limited. To study uracil excision repair in mycobacteria, we have established assay conditions using cell-free extracts of M. tuberculosis and M. smegmatis (a fast-growing mycobacterium) and oligomer or plasmid DNA substrates. We show that in mycobacteria, uracil excision repair is completed primarily via long-patch repair. In addition, we show that M. tuberculosis UdgB, a newly characterized family 5 UDG, substitutes for the highly conserved family 1 UDG, Ung, thereby suggesting that UdgB might function as backup enzyme for uracil excision repair in mycobacteria.     

Low-grade Fibromyxoid Sarcoma of the Talus: A Case Report

Low-grade fibromyxoid sarcoma is a rare tumor, which most commonly arises from the deep soft tissues of the lower extremities in young men. Diagnosis of this tumor can be difficult because of its deceptively benign histopathologic appearance. Specifically, the lesion is characterized by alternating fibrous and myxoid areas with variable cellularity and a whorled growth pattern. Like many soft tissue tumors, low-grade fibromyxoid sarcoma is also characterized by strong immunoreactivity to the human proto-oncogene BCL-2. Cytogenetically, the lesion has also been associated with the t (7,16) (q33;p11) translocation, with the characteristic resultant FUS and CREB3L2 fusion gene. In this report, we describe the rare case of a low-grade fibromyxoid sarcoma that appeared to develop as a primary malignancy in the neck of the talus of a young man who presented with recurrent ankle pain after a previous surgery for a cystic lesion at the same site.     

White piedra of scalp hair by Trichosporon inkin

White piedra is a rare fungal infection of hair and is reported to be all the more rare on scalp. Trichosporon inkin is usually associated with white piedra of pubic hair. We report a case of white piedra of scalp hair caused by T. inkin. This is the first case reported from India and the fifth case reported worldwide. A 50-year-old Muslim female presented with white knots over scalp hair. Diagnosis of Trichosporon was made by examining KOH mounts of epilated hair and Lactophenol Cotton Blue preparations of the growth in culture. Automated mini-API test (for biochemical profiles) and Electronmicroscopy studies (for cell wall structures) helped in identification of the species. Mini-API test was also positive for Cryptococcus curvatus which could be due to similarity in biochemical and physiological properties of the two species. Absence of C. curvatus on culture further supports this view. Topical antifungal therapy resulted in clinical clearance within 2 months. Higher incidence of scalp white piedra is observed in Muslim females; contributing factor being the custom of using a veil, leading to higher humidity and limited sunlight exposure.     

Choroidal neovascularization in a young,healthy eye after LASIK

BackgroundChoroidal neovascularization (CNV) is associated with age-related macular degeneration (AMD), degenerative myopia, angioid streaks, presumed ocular histoplasmosis syndrome, and numerous other ocular and systemic conditions. Idiopathic CNV is also a common form of the condition. However, CNV has rarely been noted after laser-assisted in situ keratomileusis (LASIK) and a cause-and-effect relationship has not been found. A case of CNV after uneventful LASIK is reported here, along with a literature review of previously reported cases and suggested pathophysiology. A link between LASIK and CNV is sought.MethodsA case report of CNV in a young, healthy eye after uneventful LASIK is presented. Review of the pertinent literature reporting a relationship between LASIK and CNV was conducted through 2007, and few studies are reported after 2005.ConclusionTo date, there is anecdotal evidence of CNV after LASIK. The incidence from prior reports ranges from 0.003% to 0.33%. However, a causal link cannot be disregarded and merits further study. Each patient undergoing LASIK warrants a thorough preoperative dilated fundus examination, including a thorough examination of the macula. This occurrence, albeit rare, should be considered for inclusion in the refractive surgery consent form.     

Advanced abdominal pregnancy: a search for consensus. Review of literature along with case report

Introduction

Intentional placental removal for abnormally invasive placenta (AIP) is fundamentally abandoned at planned surgery for it. Whether this holds true even after recent introduction of various hemostatic procedures is unclear.

Materials and Methods

We discussed on this issue based on our own experiences and also on the recent reports on various hemostatic procedures.

Results

Studies directly answering this question have been lacking. We must weigh the balance between the massive bleeding and possibility of uterus-preservation when intentional placental removal strategy is employed.

Conclusion

An almost forgotten strategy, the “intentional placental removal” for planned AIP surgery may regain its position when appropriate hemostatic procedures are concomitantly used depending on the situation. Even employing this strategy, quick decision to perform hysterectomy under multidisciplinary team may be important.

     

Single lens to lens duplication: the missing link

Congenital anomalies of the lens include a wide range from lens coloboma to primary aphakia and doubling of lens. There have been few case reports of double lens; the etiology suggested is metaplastic changes in the surface ectoderm that leads to formation of two lens vesicles and hence resulting in double lens. We report a case with bilobed lens, which raises the possibility of explaining the etiology of double lens.