Bioflavonoid combination attenuates diabetes-induced nephropathy in rats via modulation of MMP-9/TIMP-1, TGF-ß, and GLUT-4-associated pathways.

Background: Diabetic nephropathy represents a significant microvascular complication of diabetes, characterized by extracellular matrix accumulation, loss of cell-cell junctions, microalbuminuria, and diminished creatinine clearance. Despite its prevalence, therapeutic options dedicated to this condition are currently lacking. Natural products like bioflavonoids have garnered attention for their potential therapeutic benefits. The present study aimed to evaluate the efficacy of a bioflavonoid combination, including ginger extract, soy extract, and hesperetin, in a diabetic rat model. Methods: Diabetes was initiated in the rat pups via intraperitoneal injection of streptozotocin on the fifth postnatal day. After six weeks, rats exhibiting blood sugar levels exceeding 160 mg/dL were allocated into diabetic control and treatment groups, with eight animals each. A subset of rats received citrate buffer as a control. The treatment group received the bioflavonoid combination orally for twenty-four weeks. Various parameters, including glycemic levels, urinary parameters, antioxidant status, mRNA expression via Western blot, gel zymography, and immunohistochemistry, were assessed at the study's conclusion. Results: The bioflavonoid combination demonstrated significant reductions in hyperglycemia and various urinary parameters compared to controls. Notably, it modulated MMP-9/TIMP-1 expression, upregulated GLUT-4, and downregulated TGF-ß. Additionally, the combination enhanced total antioxidant capacity, indicating potential antioxidative benefits. Conclusions: This study highlights the therapeutic potential of a bioflavonoid combination (ginger extract, soy extract, and hesperetin) in improving renal function in diabetic nephropathy. By modulating key factors such as MMP-9/TIMP-1, TGF-ß, and GLUT-4, this combination presents a promising avenue for further exploration in managing diabetic nephropathy. These findings underscore the importance of natural products as potential therapeutic agents in addressing diabetic complications.

Lab-on-a-chip optical biosensor platform: a micro-ring resonator integrated with a near-infrared Fourier transform spectrometer.

In this paper, we demonstrated the design and experimental results of the near-infrared lab-on-a-chip optical biosensor platform that monolithically integrates the MRR and the on-chip spectrometer on the silicon-on-insulator (SOI) wafer, which can eliminate the external optical spectrum analyzer for scanning the wavelength spectrum. The symmetric add-drop MRR biosensor is designed to have a free spectral range (FSR) of ∼19 nm and a bulk sensitivity of ∼73 nm/RIU; then the drop-port output resonance peaks are reconstructed from the integrated spatial-heterodyne Fourier transform spectrometer (SHFTS) with the spectral resolution of ∼3.1 nm and the bandwidth of ∼50 nm, which results in the limit of detection of 0.042 RIU.

Comparison of lung ultrasound technique versus clinical method to evaluate the accuracy of size and placement of left endobronchial double lumen tube in patients undergoing elective thoracic surgery: a prospective observational study.

Anthropometric measurements like height and gender have been frequently found to be inaccurate in prediction of size of double lumen tube (DLT). A tracheal ultrasonography (TUS) is a technique that can be used to predict the size of DLT and its correct placement for lung isolation. We aim to check the accuracy of ultrasound over clinical methods. This prospective study included 68 patients undergoing elective thoracic surgery requiring one-lung ventilation (OLV) with DLT. The groups were assessed for the size of DLT by either anthropometric measurement using height and gender (Group C) or ultrasound method (Group U). Further, the accuracy of placement of DLT was assessed through, either lung auscultation in group C or various ultrasonographic and ventilatory parameters such as lung isolation in the first attempt (lung sliding and lung pulse sign), oxygenation status and peak airway pressure, in group U. Surgeon satisfaction score was also compared in both the groups. The accuracy of predicted DLT size between Group C and Group U was statistically significant (p=0.044). In Group C, 56% of patients showed a mismatch between the predicted DLT size and the actual size required, while in Group U, the mismatch was only 32.4%. The accuracy of DLT placement through group C was 41% as compared to 79% in Group U. Surgeon satisfaction score was also significantly higher in Group U as compared to Group C (p=0.0028). Thus, our study suggests that tracheal and chest ultrasonography for DLT size selection and placement for lung isolation is superior to clinical methods.

Development and Evaluation of Floating Microspheres of Anticonvulsant Drug by 32 Full Factorial Design.

Objectives: Present study was to develop and evaluate gastroretentive microspheres by the solvent evaporation technique. Materials and Methods: Gabapentin and HPMC K100 were used to develop the formulations. Gastroretentive microspheres were developed by the solvent evaporation technique from the preliminary batches of gabapentin microspheres batch FMG3 were selected for factorial study. Results: Factorial batches showed the mean particle size of the floating microsphere formulations for gabapentin (FFMG1-FFMG9) was in the range of 185.63 ± 0.13 to 510.04 ± 0.09 µm. The percentage yields of formulations FFMG1 to FFMG9 for gabapentin ranged from 53.5 ± 0.95 to 96.64 ± 0.42. The buoyancy percentage was calculated for the formulations and found that all formulations could float on dissolution medium for 12 h. The drug loading in gabapentin microspheres was found 65.29 ± 0.46 to 84.3 ± 0.44. The swelling study was found to be 756.34 ± 1.48 to 890.46 ± 0.78 for gabapentin. Batch FFMG6 and FFMC2 showed better drug release 99.1% and 99.25% respectively. The optimized formulation FFMG6 for gabapentin showed an n value 0.8474 and R2 value 0.9965. Conclusion: Optimized formulation obeys Korsmeyer-Peppas release. Scanning electron microscopy images of microspheres were spherical, discrete, and freely flowing. ANOVA for the given formulations showed p value less than 0.0500. The stability study indicated no significant changes in the microspheres. In radiographic images, floating microspheres were retained in the stomach of rabbits for twelve hours.

Cyclodextrin Derivative Enhances the Ophthalmic Delivery of Poorly Soluble Azithromycin.

Azithromycin (AZM), a macrolide antibiotic used for the treatment of chlamydial conjunctivitis, is less effective for the treatment of this disease due to its poor bioavailability (38%). Various alternatives have been developed for improving the physicochemical properties (i.e., solubility) of the AZM without much success. To overcome the problems associated with AZM, an inclusion complex employing a modified cyclodextrin, i.e., sulfobutylether-ß-cyclodextrin (SBE-ß-CD), was prepared and characterized by phase solubility studies and PXRD techniques. The results portrayed the formation of an inclusion complex of AZM with SBE-ß-CD in 1:2 molar stoichiometric ratios. This inclusion complex was later incorporated into a polymer matrix to prepare an in situ gel. Various combinations of Carbopol 934P and hydroxypropyl methylcellulose (HPMC K4M) polymers were used and evaluated by rheological and in vitro drug release studies. The optimized formulation (F4) containing Carbopol 934P (0.2% w/v) and HPMC K4M (0.2% w/v) was evaluated for clarity, pH, gelling capacity, drug content, rheological properties, in vitro drug release pattern, ocular irritation test, and antimicrobial efficacy. Finally, owing to the improved antimicrobial efficacy and increased residence time, the AZM:SBE-ß-CD in situ gel was found to be a promising formulation for the efficient treatment of bacterial ocular disease.

Interictal autonomic changes in persons with epilepsy (PWE) on carbamazepine (CBZ) versus other anti-seizure drug monotherapy: A cross-sectional study.

OBJECTIVE: Epilepsy is one of the most prevalent neurological conditions and carbamazepine is a commonly used anti-seizure drug (ASD), especially in developing nations. There are reports of carbamazepine causing atrioventricular conduction defects and autonomic dysfunctions and its implication in Sudden Unexpected Death in Epilepsy (SUDEP) is controversial. We planned this study to assess the effect of carbamazepine (CBZ) on autonomic function compared to other ASDs in persons with epilepsy. METHODS: In this cross-sectional study, we assessed the sympathetic and parasympathetic autonomic functions in persons with epilepsy (PWE) on CBZ versus other anti-seizure monotherapy using tests of heart rate variability including its time-, frequency- and non-linear domains, heart rate response to deep breathing, valsalva maneuver, and blood pressure response to isometric handgrip. RESULTS: Persons with epilepsy on CBZ monotherapy did not show a significant reduction in the time domain parameter SDRR compared to other ASDs used as monotherapy (mean ±â€¯SD, 38.04 ±â€¯18.75 ms vs 44.37 ±â€¯20.35 ms; p = 0.125). However, PWE on CBZ had significantly lower time-domain measurements including RMSSD (mean ±â€¯SD 31.95 ±â€¯17.29 ms vs 42.02 ±â€¯22.29 ms; p = 0.018), SDSD (mean ±â€¯SD 31.91 ±â€¯17.26 ms vs 41.96 ±â€¯22.27 ms; p 0.018), and pNN50 [median (IQR) 05.45(0.69-25.37) vs 16.38(2.32-36.83); p = 0.030]. Frequency domain measures of HRV, heart rate responses to deep breathing, valsalva maneuver and tilt-testing and BP responses to valsalva and tilt-testing were not significantly different between the groups. CONCLUSION: The findings of our study indicate reduced parasympathetic activity in persons on CBZ monotherapy compared to other ASDs, which may pose risk of SUDEP. Carbamazepine may thus be avoided in those at risk of autonomic dysfunction and SUDEP.

Electrically writable silicon nanophotonic resistive memory with inherent stochasticity.

An electrically writable resistive memory with optical readout based on silicon nanophotonic structure is proposed. Hybridization of optical and surface plasmonic modes in the device enables nanoscale optical confinement to efficiently detect the resistive memory effect in a 13 nm thick SiO2 layer sandwiched between p-type silicon and gold. Electrical write and optical readout capabilities of the proposed device are experimentally demonstrated with well-defined optical and electrical hysteresis curves at a wavelength of 1550 nm. The p-type silicon carries multifold benefits-it provides low propagation loss and a defect-free interface resulting from thermally (locally) grown oxide; the combination of p-silicon, SiO2, and gold results in a self-rectifying operation to enable the realization of a memory stack. An on-off extinction ratio of 10 dB is demonstrated for a 5 mm long device. The proposed device shows an inherent stochastic property where the set (writing) voltage reduces in each set-reset cycle, which can be used for optical readout of synaptic weight for neuromorphic computations.

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.

Minicapsules encapsulating nanoparticles for targeting, apoptosis induction and treatment of colon cancer.

Cancer therapies are aimed at eliminating the rapidly growing tumor cells by surgery and radiotherapy. The present therapies are only fruitful in early identified cases. The present study involves the preparation and characterization of eudragit S100-coated mini-capsules filled with chitosan nanoparticles-unconjugated and folic acid (FA)-conjugated encapsulating caspase 3 activator (7-hydroxystaurosporine). The formulated nanoparticles were compared for the cancer targeting and curing ability of the same by pre-investigation through drug release in organ-imitated fluids and ex vivo studies (cell viability, DNA fragmentation, caspase 3 activity), and then its confirmation through in vivo studies (tumor regression and distribution). The prepared nanoparticles were nearly spherical in shape, having positive zeta potential. From the cell line studies, it can be concluded that both the conjugated formulations showed better uptake, apoptosis, caspase 3 activation and DNA fragmentation. Stability study was performed according to ICH guidelines and formulation stored at 5° ± 3 °C was found to be most stable. The in vivo studies also supported the findings and showed better comprehensive residence time (23.61 ± 1.75 h), tumor distribution profile than UCN 01 alone. The results of in vitro, ex vivo and in vivo studies lead to the conclusion that the coated minicapsules specifically deliver the drug in the colon showing high therapeutic value and low side effects.

A Pocket-Friendly and Sustainable Iontophoresis Apparatus for Palmoplantar Hyperhidrosis: Advancement over a Previously Described Homemade Design.

INTRODUCTION AND OBJECTIVES: Tap water iontophoresis is a promising therapy for palmoplantar hyperhidrosis. Non-affordability and nonavailability of the marketed device restrict its usage for many patients hailing from villages or small cities. MATERIALS AND METHODS: In an article named "A simple user-made iontophoresis device for palmoplantar hyperhidrosis" published previously in this journal, a simple inexpensive homemade device that runs on 12 V direct current battery was described. We made a small modification by using a 220-12 V alternate current to direct current semiconductor diode-based transformer for the current supply. RESULTS: The added innovation made the device lightweight, cheaper, and usable with domestic electric supply at home/clinic. Sustained supply of current at same voltage without dip and non-requirement to change/replace battery are added advantages. Cost of the whole assembly is ₹310. Working and clinical efficacy of our device were comparable to the commercially available apparatus as reported by 13 patients who received thrice a week of 15min sessions with our device. Mild electric pricking sensation was felt by all patients. Four of thirteen reported that pricking sensation was a bit more with our device as compared to the marketed device. No calibration for intensity is available in our device. CONCLUSION: This simple to assemble and inexpensive device makes iontophoresis applicable in many needy patients with similar efficacy and few limitations compared to expensive marketed devices.

Pulmonary tuberculosis presenting as diffuse alveolar hemorrhage: Believe it or not.

Diffuse alveolar hemorrhage (DAH) has been rarely reported with pulmonary infections and even rarer with pulmonary tuberculosis (PTB). We hereby report the case of a 31-year-old male, a known case of ankylosing spondylitis, who presented with clinical and radiological features consistent with DAH. Initial partial improvement with steroids was followed by a microbiological diagnosis of tuberculosis (TB). Starting of antituberculous treatment was followed by complete clinical improvement. This leads to a thought-provoking possible association between the two pathologies, DAH and PTB, if any.

Analysis and Clinical Importance of Skull Base Fractures in Adult Patients with Traumatic Brain Injury.

AIMS AND OBJECTIVES: Basal skull fracture (BSF) is rare in head injury (HI) patients and occasionally goes unnoticed which may lead to cerebrospinal fluid (CSF) fistula. With changing trends in HI, there is a need to reassess incidence and pattern of BSF pattern, CSF leak, meningitis, and management protocol, especially in this part of the world where detailed literature is lacking. SUBJECTS AND METHODS: We closely followed adult patients admitted with BSF in our institute between January 2013 and December 2014. Associated clinical features were recorded. In case of CSF leak, detailed CSF study was done and patients were managed accordingly. Patients with persistent CSF leak were managed surgically. RESULTS: During the study period, 194 of 5041 HI patients had evidence of BSF (3.85%). BSF was most commonly associated with moderate-to-severe HI (73.19%). About 81.44% patients were male and 29.9% were <30 years. Most common cause was road traffic accident (84.54%). Isolated anterior cranial fossa (ACF) fracture was most common (50%). About 63.92% patients had raccoon eyes. Forty-three patients had CSF leak with CSF rhinorrhea being more common. Culture of only 5 patients suggested bacterial meningitis. CSF leak lasted for more than 10 days in 8 patients, of which 4 patients required surgical repair. CONCLUSIONS: BSF is rare in victims of HI. It is more common in young adult males. ACF fractures are most common in our setup. Clinical signs of BSF are supportive but not definitive; high resolution computed tomography head is gold standard to detect BSF. CSF leak is rare and most of the cases can be managed conservatively. Leak persisting more than 7-10 days has high risk of developing meningitis and likely to need surgical intervention.

Safety of important dermatological drugs (retinoids, immune suppressants, anti androgens and thalidomide) in reproductively active males with respect to pregnancy outcome: A brief review of literature.

Paternally transmitted damage to offspring is recognized as a complex issue. Each parent contributes 23 chromosomes to a child; hence, it is necessary to know the effects of both maternal and paternal pre-and peri-conceptional exposure to drugs on pregnancy outcome. While there are many studies on the effects of maternal drug exposure on pregnancy outcome, literature on paternal exposure is scarce. Of late however, paternal exposure has been receiving increasing attention. We present a brief review on the safety of commonly used drugs in dermatology, focused on retinoids, immune suppressants, anti androgens and thalidomide.

Topical Delivery of Erythromycin Through Cubosomes for Acne.

BACKGROUND: Topical delivery is an attractive route for local and systemic treatment. The novel topical application has many advantages like averting the GI-irritation, preventing the metabolism of drugs in the liver and increasing the bioavailability of the drug over the conventional dosage forms. OBJECTIVE: The aim of present work was to prepare and characterized erythromycin encapsulated cubosomes using different concentrations of glyceryl monooleate and poloxamer 407 by the emulsification method. METHODS: The prepared dispersion of cubosomes was characterized for surface morphology, particle size, entrapment efficiency and in vitro release. Further, optimized formulation was converted to cubosomal gel by incorporating carbopol 934 at different concentrations. The prepared gel was characterized for homogeneity, pH, viscosity, spreadibility, drug content and in vitro drug release study. RESULTS: The result of optimized cubosomes showed average particle size of 264.5±2.84nm and entrapment efficiency about 95.29±1.32 % and the pH of optimized cubosomal was found to be 6.5, viscosity 2475-8901(cp), drug content 95.29% and the spreadability was found to be 11.74 gm.cm/sec. The in vitro drug release kinetics of optimized formulation was found to follow Korsmeyer peppas model having highest R2 value 0.835 and in vitro drug release of optimized erythromycin loaded cubosomal gel and plain drug gel in 24 hr was found to be 89.91±0.73 and 88.64±2.16, while in 36 hr plain drug gel and cubosomal gel showed drug release about 87.64±0.97 and 91.55±1.09, and sustained release was obtained after 24 hr in case of cubosomal gel. CONCLUSION: Thus, as a whole it can be concluded that erythromycin loaded cubosomes are effective in topically delivering drug in sustained and non-invasive manner for treatment and prevention of acne.

Rationale Behind the Use of Double-Layer Polypropylene Patch (G-patch) Dural Substitute During Decompressive Craniectomy as an Adhesion Preventive Material for Subsequent Cranioplasty with Special Reference to Flap Elevation Time.

OBJECTIVE: Dural substitutes are used in decompressive craniectomy (DC) to prevent adhesions during subsequent cranioplasty. Current literature attributes them to reduced blood loss and reduction in operative time of cranioplasty. The use of double-layer substitute has rarely been documented. We studied the use of double-layer G-patch as a dural substitute in DC and evaluated its outcome during subsequent cranioplasty with special focus on flap elevation time and blood loss during cranioplasty. METHODS: We performed emergency frontotemporoparietal decompressive craniectomy using a double layer of G-patch as dural substitute. Subsequent cranioplasty was done in these 35 patients. The development of adhesion formation between the tissue layers, amount of blood loss, and flap elevation time were recorded. RESULTS: During the cranioplasty, a clear and smooth plane of dissection was found between the 2 layers of G-patch in all cases. Average flap elevation time was 21.8 minutes, and average time taken for cranioplasty was 124.12 minutes. Average blood loss was 83 mL. None of the patients required re-exploration for infection of bone flap or postoperative bleed. CONCLUSIONS: While evaluating the use of dural substitute during DC as an adhesion preventive material for subsequent cranioplasty, flap elevation time and blood loss should be taken into account rather than operative time. Double-layer G-patch during DC facilitates subsequent cranioplasty by preventing adhesions between the layers, resulting in easier dissection and reduced blood loss.