Furan oligomers and beta-carbolines from terrestrial streptomycetes

2,5-Bis(hydroxymethyl)furan monoacetate (3) and 2,5-bis(hydroxymethyl)furan diacetate (4) were obtained as new natural products from an ethyl acetate extract of the terrestrial Streptomyces sp. isolate GW11/1695. Another Streptomyces isolate, GW21/1313, delivered a dimer (6) and a trimer (7) of (hydroxymethyl)furfural. The latter strain also produced 4-hydroxy-2-(5-(hydroxymethyl)furan-2-ylmethylene)-5-methylfuran-3-one (5), perlolyrin (8), and two new beta-carboline derivatives, 9 and 10. 2,5-Bis(hydroxymethyl)furan diacetate (4) exhibited weak cytotoxic activity against brine shrimp larvae.     

Vitamin D Status among Women in a Rural District of Nepal: Determinants and Association with Metabolic Profile—A Population-Based Study

Hypovitaminosis D is prevalent worldwide, and especially in South-Asia. According to the Institute of Medicine (IOM), 25(OH)D levels below 30 nmol/L are defined as vitamin D deficiency (VDD) and levels between 30–50 nmol/L as insufficiency (VDI). Besides its role in calcium homeostasis, it has been postulated that vitamin D is involved in metabolic syndrome. Given the scarcity of data on vitamin D status in Nepal, we aimed to examine the prevalence of VDD and VDI, as well as the determinants and association with metabolic parameters (lipids, HbA1c), in a cohort of women in rural Nepal. Altogether, 733 women 48.5 ± 11.7 years of age were included. VDD and VDI were observed in 6.3 and 42.4% of the participants, respectively, and the prevalence increased by age. Women reporting intake of milk and eggs > 2 times weekly had higher 25(OH)D levels than those reporting intake < 2 times weekly. Women with vitamin D levels < 50 nmol/L displayed higher levels of cholesterol, LDL-cholesterol, triglycerides, and HbA1c. Additionally, a regression analysis showed a significant association between hypovitaminosis D, dyslipidemia, and HbA1c elevation. In conclusion, VDI was prevalent and increased with age. Milk and egg intake > 2 times weekly seemed to decrease the risk of VDI. Moreover, hypovitaminosis D was associated with an adverse metabolic profile.     

Evaluation of cytotoxic, oxidative stress, proinflammatory and genotoxic responses of micro- and nano-particles of dolomite on human lung epithelial cells A(549)

Dolomite is a natural mineral of great industrial importance and used worldwide, thus millions of workers are at risk of occupational exposure. Its toxicity is however, meagerly documented. In the present investigation, a dolomite powder obtained from its milling unit was analyzed by some standard methods namely, optical microscopy, transmission electron microscopy and dynamic light scattering. Results showed that dolomite powder contained particles of different shapes and size both microparticles (MPs) and nanoparticles (NPs), suggesting potential occupational exposure of these particles. An attempt was therefore, made to investigate dolomite toxicity in a particle size-dependent manner in human lung epithelial cells A(549). The comparative toxicity evaluation of MPs and NPs was carried out by assessing their effects on cell viability, membrane damage, glutathione, reactive oxygen species (ROS), lipid peroxidation (LPO), micronucleus (MN) and proinflammatory cytokines, namely tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). These markers of cytotoxicity, genotoxicity and inflammation were assayed in cells exposed to MPs and NPs in a dose-and time-dependent manner. Invariably, their toxic effects were dose-and time-dependent while NPs in general were significantly more toxic. Notably, NPs caused oxidative stress, genotoxicity and inflammatory responses, as seen by significant induction of ROS, LPO, MN, TNF-α, IL-1β and IL-6. Thus, the study tends to suggest that separate health safety standards would be required for micrometer and nanometer scale particles of dolomite.     

Computer-Based Identification of Type 2 Diabetic Subjects with and Without Neuropathy Using Dynamic Planter Pressure and Principal Component Analysis

Diabetes is a chronic disease that is characterized by an increased blood glucose level due to insulin resistance. Type 2 diabetes is common in middle aged and old people. In this work, we present a technique to analyze dynamic foot pressures images and classify them into normal, diabetes type 2 with and without neuropathy classes. Plantar pressure images were obtained using the F-Scan (Tekscan, USA) in-shoe measurement system. We used Principal Component Analysis (PCA) and extracted the eigenvalues from different regions of the foot image. The features extracted from region 1 of the foot pressure image, which were found to be clinically significant, were fed into the Fuzzy classifier (Sugeno model) for automatic classification. Our results show that the proposed method is able to identify the unknown class with an accuracy of 93.7%, sensitivity of 100%, and specificity of 83.3%. Moreover, in this work, we have proposed an integrated index using the eigenvalues to differentiate the normal subjects from diabetes with and without neuropathy subjects using just one number. This index will help the clinicians in easy and objective daily screening, and it can also be used as an adjunct tool to cross check their diagnosis.     

Occult pretransplantation systemic inflammation and posttransplantation vascular changes in a primate arterial allograft model

BACKGROUND: Occult systemic inflammation, as manifested by increased levels of C-reactive protein (CRP), identify patients at increased risk for renal allograft rejection. The mechanisms linking occult systemic inflammation to these adverse outcomes remain unclear. The purpose of this study was to examine the anatomic and physiologic effects of occult pretransplantation systemic inflammation on posttransplantation allograft outcome in a nonhuman primate model. METHODS: Seventy-one healthy male Rhesus macaques were stratified into quartiles based on serum CRP. Five high quartile and six low quartile animals underwent common iliac artery transplantation from male donors. Duplex ultrasound measured graft flow at 3 weeks postoperatively; luminal narrowing was assessed by graft/femoral peak systolic velocity ratio. At 6 weeks, the grafts were harvested and morphometry studies were performed. Vessel wall changes were assessed by measuring the intimal medial area. RESULTS: The allografts placed in high CRP quartile animals had more luminal narrowing by 3 weeks than those placed in low quartile animals, as evidenced by a higher mean graft/femoral peak systolic velocity ratio (1.6 vs. 0.90, P=0.006). Morphometry studies after graft harvest showed increased vessel wall area in the high quartile group versus the low quartile group (1.39 mm vs. 1.03 mm, P=0.018). CONCLUSIONS: Occult pretransplantation systemic inflammation is associated with increased intimal thickening and stenosis after arterial allograft transplantation in a primate model. Additional studies are needed to confirm these results and to further investigate potential mechanisms linking pretransplantation systemic inflammation to adverse outcomes after transplantation.     

Two in one: Double free flap from a single free fibula osteocutaneous unit

In the past two decades, the advancement in the microsurgical techniques has revolutionised the reconstruction of post-oncological head and neck defects. Free fibula osteocutaneous flap (FFOCF) has been considered as the treatment of choice by many for mandible reconstruction. The improvement in the surgical resection and adjuvant treatment has improved the survival rates even in patients with advanced cancer. Simultaneously the reconstruction is addressed towards more functional and aesthetic aspects to improve the quality of life in these patients. In this respect, a double free flap is advocated in certain cases of extensive composite oromandibular defects (COMDs). But in our institute, we have managed two such cases of extensive COMD with a single FFOCF unit – fibula bone with a skin paddle for inner lining and a perforator-based skin paddle from the proximal part of the FFOCF unit, anastomosed separately for outer cover. Compared to two separate free flaps, this method has the advantage of single donor site and reduction in reconstruction time. Though the technique of divided paddle, deepithelisation and supercharging has been mentioned for FFOCF, no such clinical cases of two free flaps from a single FFOCF unit have been mentioned in the literature.KEY WORDS: Composite oromandibular defect, double free flap, free fibula osteocutaneous flap     

Experience with tacrolimus in children with steroid-resistant nephrotic syndrome

Children with steroid-resistant nephrotic syndrome (SRNS) are at risk of developing renal failure. We report here the results of a single-center retrospective observational study of the remission rate in pediatric patients with SNRS receiving tacrolimus. Serial renal biopsies from children on tacrolimus therapy were evaluated for tubulointerstitial fibrosis and transforming growth factor-β immunostaining. Of the 16 children with SRNS, 15 went into complete remission after a median of 120 days of therapy. Nine children were able to stop steroids, while the others were on tapering doses. Forty-seven percent had relapses, most of which were steroid-responsive. Serial renal biopsies were obtained from seven children after a median treatment duration of 24 months; two of these children had increased tubulointerstitial fibrosis and four showed increased transforming growth factor-β tissue staining. Children with worsening histological findings were younger. There was no significant association between tacrolimus exposure and biopsy changes, although the average trough level was higher in those children with worsening histological findings. In conclusion, tacrolimus may be a safe and effective alternative agent for inducing remission in children with SRNS. However, caution needs to be taken when prescribing this agent due to its narrow therapeutic index. Serial renal biopsies are necessary to check for subclinical nephrotoxicity, especially in younger children and those with higher trough levels.     

The Broad Spectrum of Quality in Deceased Donor Kidneys

The quality of the deceased donor organ clearly is one of the most crucial factors in determining graft survival and function in recipients of a kidney transplant. There has been considerable effort made towards evaluating these organs culminating in an amendment to allocation policy with the introduction of the expanded criteria donor (ECD) policy.
Our study, from first solitary adult deceased donor transplant recipients from 1996 to 2002 in the National Scientific Transplant Registry database, presents a donor kidney risk grade based on significant donor characteristics, donor–recipient matches and cold ischemia time, generated directly from their risk for graft loss. We investigated the impact of our donor risk grade in a naïve cohort on short- and long-term graft survival, as well as in subgroups of the population.
The projected half-lives for overall graft survival in recipients by donor risk grade were I (10.7 years), II (10.0 years), III (7.9 years), IV (5.7 years) and V (4.5 years). This study indicates that there is great variability in the quality of deceased donor kidneys and that the assessment of risk might be enhanced by this scoring system as compared to the simple two-tiered system of the current ECD classification.     

Anterior minimally invasive approaches for the cervical spine

The percutaneous endoscopic discectomy (PECD) with working channel endoscope (WSH) endoscopy set could be a safe and effective minimally invasive surgical option for non-contained cervical disc herniation in selected patients. Judicious use of the end-firing Ho: Yttrium-Aluminium-Garnet (YAG) laser for both decompressive and thermoannuloplasty effect during the percutaneous endoscopic cervical annuloplasty (PECA) is mandatory in order to prevent possible injury to spinal cord or root. Although the percutaneous cervical stabilization (PCS) using the cervical B-Twin may not completely replace the cervical arthrodesis, this minimally invasive procedure can preserve anterior structures and thereby retain segmental stability and prevent the possible kyphotic progression after fusion surgery. To our knowledge, these minimally invasive procedures for cervical spine disease may serve to minimize surgery-induced complications associated with anterior cervical discectomy and fusion (ACDF).     

Sinus pericranii with unusual features: multiplicity, associated dural venous lakes and venous anomaly, and a lateral location

Anomalous connections between an extracranial venous sac and intracranial dural sinuses through dilated diploic and emissary veins of the skull result in sinus pericranii (SP). In this study, two patients with the rare presentation of multiple, congenital SP with associated dural venous lakes and venous anomalies are described. In one patient, multiple SPs were located in the frontal, parasagittal region with an associated subcortical venous angioma; and, in the other, peritorcular and juxta–transverse–sigmoid sinus junction SP coexisted. The venous anomalies drained into venous lakes in close proximity to major sinuses. They also communicated with extracranial tributaries via interosseous veins leading to the development of venous hypertension that presumably caused pressure erosion of the skull. This may have been responsible for the pathogenesis of multiple subgaleal venous sacs of SP and may also lead to profuse hemorrhage, cortical venous thrombosis, or air embolism. Multiplicity, associated venous lakes, venous angioma, and a lateral location are unique presentations of SP. Sac excision, transcranial venous anastomotic channel blockage, and reinforcement/replacement of the underlying bone are the recommended modalities of treatment.