Domain crossover in the reductase subunit of NADPH-dependent assimilatory sulfite reductase.

NADPH-dependent assimilatory sulfite reductase (SiR) from Escherichia coli performs a six-electron reduction of sulfite to the bioavailable sulfide. SiR is composed of a flavoprotein (SiRFP) reductase subunit and a hemoprotein (SiRHP) oxidase subunit. There is no known high-resolution structure of SiR or SiRFP, thus we do not yet fully understand how the subunits interact to perform their chemistry. Here, we used small-angle neutron scattering to understand the impact of conformationally restricting the highly mobile SiRFP octamer into an electron accepting (closed) or electron donating (open) conformation, showing that SiR remains active, flexible, and asymmetric even with these conformational restrictions. From these scattering data, we model the first solution structure of SiRFP. Further, computational modeling of the N-terminal 52 amino acids that are responsible for SiRFP oligomerization suggests an eight-helical bundle tethers together the SiRFP subunits to form the SiR core. Finally, mass spectrometry analysis of the closed SiRFP variant show that SiRFP is capable of inter-molecular domain crossover, in which the electron donating domain from one polypeptide is able to interact directly with the electron accepting domain of another polypeptide. This structural characterization suggests that SiR performs its high-volume electron transfer through both inter- and intramolecular pathways between SiRFP domains and, thus, cis or trans transfer from reductase to oxidase subunits. Such highly redundant potential for electron transfer makes this system a potential target for designing synthetic enzymes.

A rare case of clomiphene-induced leukocytoclastic vasculitis.

Clomiphene citrate is a first-line drug for the induction of ovulation in infertility cases. Leukocytoclastic vasculitis (LCV) is an extremely rare serious adverse drug reaction to clomiphene. We report here the case of a 30-year-old Indian female patient who presented with generalized petechiae and palpable purpura without fever and sparing the mucosa, temporally related to clomiphene intake and consistent with LCV histologically. Clomiphene was stopped and the patient was treated symptomatically with prednisolone 40 mg/day, oral levocetirizine 5 mg twice daily, and emollients and calamine lotion topically. The patient improved over 3-4 weeks. The prednisolone dose was tapered weekly and withdrawn gradually. To date, drug-induced LCV has not been previously reported with clomiphene. Although rare, clomiphene could be considered a potential cause of drug-induced cutaneous LCV in the differential diagnosis of erythematosus rash with non-blanching petechiae and purpura.

Comparison of Clinical Effectiveness and Safety of Newer Nonsteroidal Anti-inflammatory Drugs in Patients of Osteoarthritis of Knee Joint: A Randomized, Prospective, Open-label Parallel-group Study.

OBJECTIVE: Osteoarthritis (OA) is a chronic progressive degenerative disease of weight-bearing joints and the leading cause of disability in elderly. Current medical management of OA is mostly palliative with nonsteroidal anti-inflammatory drugs (NSAIDs) being the mainstay of therapy. Reports of gastrointestinal adverse effects with traditional NSAIDs and cardiovascular adverse effects associated with selective cyclooxygenase-2 (COX-2) inhibitors have prompted the hunt for a better NSAID with no or minimal adverse effects. This study compares the clinical effectiveness and safety of newer NSAIDS etodolac and lornoxicam to diclofenac which has been a standard therapy in patients of OA of knee joint. MATERIALS AND METHODS: It was a randomized, prospective, open-label, parallel-group study conducted in 90 patients of OA of knee joint diagnosed according to the American College of Rheumatology criteria. After obtaining the informed consent, they were randomized in three groups of 30 patients each who received tablet etodolac 400 mg b.i.d, tablet lornoxicam 8 mg b.i.d, and tablet diclofenac sodium 50 mg t.i.d, respectively. The duration of the study was 12 weeks. Data were tabulated and analyzed using analysis of variance (ANOVA) test, and level of significance was determined by its P value. RESULTS: After 12 weeks of treatment, pain intensity and functional indices in terms of visual analog scale and Western Ontario and McMaster Universities Osteoarthritis score were significantly better (P < 0.05) in lornoxicam group as compared to etodolac or diclofenac group along with lesser rate of adverse effects. CONCLUSION: It was concluded that lornoxicam was more effective and better tolerated NSAID than etodolac and diclofenac in treatment of knee joint OA.

Glomus Tumor - A Rarity; M.R.I- A big help in early Diagnosis.

INTRODUCTION: Glomus tumor is a rare benign tumor arising from neuroarterial plexus concentrated beneath the nailbed usually in women of age group 20-40 yrs. The plexus is an arteriovenous anastomosis functioning without intermediary capillary bed, we report a case of glomus tumor affecting the nailbed of left little finger with characteristic periodic, spontaneous excruciating pain and temperature related algesia for the last 6 months. MRI helped in clinching the diagnosis at an early stage. Patient was operated for excision of the tumor making her completely pain free after resection oftumor. CASE PRESENTATION: A 40-year-old female patient came in Ortho. OPD with complaints of pain, cold algesia, and point tenderness on the radial side of base of the nailbed of left little finger for the last 6 months. Diagnosis was delayed despite the patient having sought the advice from different clinicians a number of times before coming to us. Pain used to occur on accidental touching of tender spot, cold water immersion; excruciating at times, making the patient faint. On physical examination clinical diagnosis of glomus tumor was made, which was confirmed on MRI as the plain X-ray was non-contributory. CONCLUSION: Most of the glomus tumors are benign, which are amenable to cure with complete surgical excision. Rarely, if the lesion exceeds 2 cm malignant transformation of the tumor must be suspected unless proven otherwise. Delay in clinical diagnosis due to dithering on the part of the clinician unnecessarily prolong the suffering in the patient which can be greatly helped by M.R.I in clinching the diagnosis early.

A rare case of isoniazid-induced erythroderma.

Tuberculosis is a common infectious disease in developing countries. Isoniazid is established the first-line antitubercular drug and an essential component of all antitubercular regimens. Erythroderma caused by isoniazid is an uncommon but serious adverse drug reaction. We report here a case of a 63-year-old female patient who presented with generalized redness and scaling with itching after 8 weeks of antitubercular treatment (ATT). ATT was stopped immediately, and antihistaminics were started. The patient improved over a period of 2 weeks. On sequential rechallenge, she developed similar lesions all over the body with isoniazid, hence confirming the diagnosis of isoniazid-induced erythroderma.

Complex Open Distal Femur Fracture Managed By Primary Autogenous Fibular Graft in Conjunction with DFLP- A Case Report.

Fractures of the distal part of the femur account for 7% of all femoral fractures. They are complex injuries that are difficult to manage; despite advances in technique and improved implants, treatment remains a challenge in many situations. An 18-year-old boy presented with an open fracture of the femur with bone loss. After initial emergency management, patient was given skeletal traction and kept on bohler braun splint. Regular antiseptic dressings of loosely stitched wound were done and intravenous antibiotics given. After 2 weeks when wound healed and twice cultures from wound site were negative, the fractured femur was stabilized with a dflp along with an autogenous free fibular graft and cortico-cancellous graft to bridge the bone defect. At one-year follow-up, fracture united with incorporation of free fibular graft. An autogenous free fibular graft in conjunction with a dflp is a viable option to manage bone defects in complicated supracondylar fractures of the femur.