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Background Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation, pain, and progressive disability. Identifying biomarkers that accurately reflect disease severity is crucial for effective management. Interleukin-6 (IL-6) is a pro-inflammatory cytokine involved in the pathogenesis of RA, and the systemic immune-inflammation index (SII) is emerging as a useful marker of systemic inflammation. This study aims to explore the relationship between serum IL-6 levels, SII, and various biomarkers to better predict disease severity in RA patients. Objective To determine the relationship between serum IL-6 levels and the SII, along with various biomarkers, across different severity levels for predicting the severity of RA in patients. Methods This cross-sectional, observational study was conducted at the Mardan Medical Complex from January 2024 to August 2024, involving 67 RA patients. Clinical assessments included demographic data, disease activity (DAS28), pain (VAS), joint damage (Larsen score), and functional status (HAQ-DI). Serum IL-6 levels, along with other biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the SII, were measured through fasting blood samples. Statistical analyses, including density plots, scatter plots, boxplots with ANOVA, and random forest models, were performed to explore associations between IL-6 and all other variables. Significance was set at p < 0.05. Results The study included 67 RA patients (mean age: 41.79 ± 10.51 years, 53.73% male). Elevated IL-6 levels (mean: 80.28 ± 35.27 pg/mL) were strongly associated with disease severity. Patients with DAS28 > 5.5 had IL-6 levels over 100 pg/mL, while those in remission had around 40 pg/mL. IL-6 levels correlated with joint damage (100 pg/mL in severe cases) and pain (over 120 pg/mL for severe pain). Patients with metabolic and cardiovascular comorbidities had the highest IL-6 levels, particularly with diabetes and hypertension (98.6 pg/mL) or cardiovascular disease (119.3 pg/mL). IL-6 correlated strongly with CRP (r = 0.65), ESR (r = 0.51), and SII (r = 0.62). Regression confirmed IL-6 as an independent predictor of severity (p < 0.001), with comorbidities being key predictors. Conclusion Elevated IL-6 and SII levels serve as critical markers for predicting the severity of RA. Addressing these markers may lead to more targeted and effective therapeutic strategies for managing disease progression., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Medical Teaching Institution Bacha Khan Medical College issued approval 634/BKMC. This is to certify that Ethical Approval has been granted to Dr. Zahir Khan, Assistant Professor, Department of Orthopedics, at Bacha Khan Medical College/Mardan Medical Complex Mardan, KP, Pakistan. Title for his article: "Relationship Between Serum Interleukin-6 Levels, Systemic Immune-Inflammation Index, and Other Biomarkers Across Different Rheumatoid Arthritis Severity Levels". Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This study was supported by Pro-Gene Diagnostics and Research Laboratory, which provided funding for the biomarker analysis. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Zeb et al.)

Biosensing, a promising branch of exploiting nanophotonic devices, enables meticulous detection of subwavelength light, which helps to analyze and manipulate light-matter interaction. The improved sensitivity of recent high-quality nanophotonic biosensors has enabled enhanced bioanalytical precision in detection. Considering the potential of nanophotonics in biosensing, this article summarizes recent advances in fabricating nanophotonic and optical biosensors, focusing on their sensing function and capacity. We typically classify these types of biosensors into five categories: phase-driven, resonant dielectric nanostructures, plasmonic nanostructures, surface-enhanced spectroscopies, and evanescent-field, and review the importance of enhancing sensor performance and efficacy by addressing some major concerns in nanophotonic biosensing, such as overcoming the difficulties in controlling biological specimens and lowering their costs for ease of access. We also address the possibility of updating these technologies for immediate implementation and their impact on enhancing safety and health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Javaid, Iqbal, Javeed, Maidin, Morsy, Shati and Choi.)

Background: Venous thromboembolism (VTE) is a widespread and significant cause of morbidity and mortality on a global scale. The primary objective of this cross-sectional study is to examine the impact of anticoagulant therapy on major organ hemorrhage events in patients diagnosed with acute venous thromboembolism (VTE). Specifically, this research compares the effects of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs)., Materials and Methods: This retrospective observational study examined the medical records of 46 patients who had been diagnosed with VTE and were receiving treatment with DOACs or VKAs. The documentation of patient characteristics encompassed demographic information, comorbidities, and treatment particulars. Within 30 days of hospital admission, the incidence of significant organ bleeding events, with an emphasis on gastrointestinal and intracranial hemorrhage, was the primary outcome evaluated., Results: Overall, 46 patients with VTE who were treated with oral anticoagulation therapy participated in the study. Twenty-four and 22 patients were administered VKAs and DOACs, respectively. The similarity in baseline characteristics between the DOAC and VKA groups ensured that the analyses were well-matched. The examination of bleeding sites unveiled subtle variations, as the DOAC group exhibited a progressive increase in the incidence of intracranial bleeding (12, 55.5%), while the VKA group demonstrated a surge in upper gastrointestinal bleeding (12, 50%) as well. While lacking statistical significance, these observed patterns are consistent with prior research that indicates that DOACs may have a lower risk of catastrophic hemorrhage in comparison to VKAs. The overall in-hospital mortality rate for patients treated with VKA was 33.3% (n=8), while that treated with DOAC was 18.2% (n=4). These differences did not reach statistical significance (P>0.05). In a similar vein, the evaluation of mortality associated with hemorrhage revealed six (25%) in the group receiving VKA and three (13.6%) in the group receiving DOAC; the P value was not statistically significant (P>0.05)., Conclusions: This study contributes valuable insights into bleeding outcomes associated with anticoagulant therapy for acute VTE. The nuanced differences in bleeding patterns highlight the complexity of anticoagulant selection, emphasizing the importance of considering bleeding site considerations. The comparable mortality rates support existing evidence regarding the favorable safety profile of DOACs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Javaid et al.)

A challenge remains in achieving adequate surface roughness of SLM fabricated interior channels, which is crucial for fuel delivery in the space industry. This study investigated the surface roughness of interior fine flow channels (1 mm diameter) embedded in SLM fabricated TC4 alloy space components. A machine learning approach identified layer thickness as a significant factor affecting interior channel surface roughness, with an importance score of 1.184, followed by scan speed and laser power with scores of 0.758 and 0.512, respectively. The roughness resulted from thin layer thickness of 20 µm, predominantly formed through powder adherence, while from thicker layer of 50 µm, the roughness was mainly due to the stair step effect. Slow scan speeds increased melt pools solidification time at roof overhangs, causing molten metal to sag under gravity. Higher laser power increased melt pools temperature and led to dross formation at roof overhangs. Smaller hatch spaces increased roughness due to overlapping of melt tracks, while larger hatch spaces reduced surface roughness but led to decreased part density. The surface roughness was recorded at 34 µm for roof areas and 26.15 µm for floor areas. These findings contribute to potential adoption of TC4 alloy components in the space industry.

Nanoparticles based TDDS was employed to overcome the adverse effects of oral contraceptives. A transdermal patch of Ethinyl Estradiol (EE) nanoparticles was aimed to provide sustained release of the drug and lower dosage frequency. The patch was designed with Eudragit-based polymeric films or EE-loaded chitosan nanoparticles poured onto a polyvinyl alcohol backing membrane, with a non-ionic surfactant (span-20) and a plasticizer (n-butyl phthalate) using solvent evaporation method. Nanoparticles were analyzed for their size, morphology, yield and entrapment efficiency. The patches were analyzed for their folding endurance, thickness, weight, drug content, in vitro release pattern, FTIR and DSC. All patches were transparent, having a uniform, smooth surface. The folding endurance of all the patches indicated optimum flexibility. In vitro, release and Ex-Vivo permeation studies showed that F1 containing nanoparticles exhibited the most optimum drug release in 72h (97.6%). The release pattern demonstrated was diffusion controlled. FTIR, DSC studies indicated no interaction between drug and excipients. The accelerated stability studies were performed at 40 ᵒ C and 70% relative humidity for six months. The product was found stable. The developed patches of EE nanoparticles were expected to improve patient compliance by reducing dose frequency and provide optimum therapy by sustained drug release for contraception.

The current research was conducted to extract the bioactive compounds from citrus waste and assess their role in the development of functional foods to treat different disorders. The scientific name of citrus is Citrus L. and it belongs to the Rutaceae family. It is one of the most important fruit crops that is grown throughout the world. During processing, a large amount of waste is produced from citrus fruits in the form of peel, seeds, and pomace. Every year, the citrus processing industry creates a large amount of waste. The citrus waste is composed of highly bioactive substances and phytochemicals, including essential oils (EOs), ascorbic acid, sugars, carotenoids, flavonoids, dietary fiber, polyphenols, and a range of trace elements. These valuable compounds are used to develop functional foods, including baked products, beverages, meat products, and dairy products. Moreover, these functional foods play an important role in treating various disorders, including anti-aging, anti-mutagenic, antidiabetic, anti-carcinogenic, anti-allergenic, anti-oxidative, anti-inflammatory, neuroprotective, and cardiovascular-protective activity. EOs are complex and contain several naturally occurring bioactive compounds that are frequently used as the best substitutes in the food industry. Citrus essential oils have many uses in the packaging and food safety industries. They can also be used as an alternative preservative to extend the shelf lives of different food products.

Fenbfen is used for pain, pyrexia and in the management of osteoarthritis, rheumatoid arthritis and other musculoskeletal disorders. The present research was planned to examine the immunomodulatory activity of fenbufen in different models of cell-mediated immunity (CMI) and humoral immunity (HI). The CMI was evaluated by delayed-type hypersensitivity (DTH) and cyclophosphamide-induced neutropenia assays while HI was appraised by hemagglutination (HA) assay by administering fenbufen at 2, 6 and 10 mg.kg-1 and azathioprine 40 mg.kg-1 (as standard therapy) to albino mice by intraperitoneal route. The ex vivo immunomodulatory action was determined by red blood cell (RBC) membrane stabilization and protein denaturation assays. The results showed that fenbufen treatment had significantly (p<0.05-p<0.001) reduced white blood cells, hemoglobin content, and red blood cells in the healthy and neutropenic mice. A significant (p<0.001) reduction in activities of superoxide dismutase and catalase and glutathione contents, and enhancement of malondialdehyde level were observed in neutropenic mice that were restored by fenbufen treatment. It suppressed DTH reaction after 24, 48 and 72 h post topical application of 2, 4-dinitrofluorobenzene (DNFB). Fenbufen or azathioprine treated groups also showed a significant reduction in the antibody titer against human RBCs induced immune activation in mice as compared to the disease control mice. Fenbufen showed IC50 of 14.0, 50.5 and 66.2 μg.ml-1 whereas, diclofenac sodium showed IC50 of 61.0, 126 and 50.5 μg/ml in RBCs membrane stabilization, egg albumin and bovine serum albumin denaturation assays respectively. The current study shows that fenbufen might have potential immunomodulatory activity against CMI and HI. It can be utilized to treat immune system disorders.

The current work was performed to explore the pharmacological mechanisms involved in the management of asthma and hypertension along with the safety profile of the Ceratonia siliqua (C. siliqua/Carob) pods. The bronchorelaxant, vasorelaxant, and cardioselective activities of C. siliqua pods were investigated using isolated rabbit tracheal, aortic, and paired atrial fragments on the Power lab data acquisition system. Normotensive rats were used to study antihypertensive activity. The plant extract and its fractions relaxed the carbachol-induced contraction in the tracheal fragments and shifted the concentration-response curve of carbachol towards the right confirming the muscarinic receptor antagonist activity. The relaxation of phenylephrine-induced contraction in an aortic fragment by the extract showed α- adrenergic blocking activity. Furthermore, the extract produced a cardio-selective response in the paired atria and decreased the blood pressure in anesthetized normotensive rats. The plant extract proved to be non-toxic in oral acute and chronic toxicity studies and did not demonstrate any sign of histopathological lesions. These results suggested that the plant extract was non-toxic and could be used in the management of lifetime therapies of respiratory and cardiovascular disorders without any unwanted effects.

Background & Objective: Peganum harmala has been traditionally used to manage rheumatoid arthritis (RA) and other inflammatory conditions. However, its use against RA has not been scientifically evaluated. The current study was designed to assess the anti-arthritic and anti-inflammatory activities of the methanolic extract of P. harmala leaves by in vitro and in vivo methods., Methods: The in vitro assays were carried out to determine the effect of plant extract on inhibition of egg albumin denaturation and human red blood cell membrane (HRBC) stabilization. Moreover, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity was performed to determine the antioxidant potential. In vivo anti-arthritic activity was performed by determining the curative effect against Complete Freund's adjuvant (0.1 ml). The plant extract was administered to rats orally at 200, 400 and 600 mg/kg/day for 21 days., Results: The values of IC50 of plant extract in protein denaturation, stabilization of HRBC and DPPH assays were 77.54 mg/ml, 23.90 mg/ml and 58.09 μg/ml, respectively. Moreover, the plant extract significantly attenuated the poly-arthritis and weight loss, anemia and paw edema. The plant extract restored the level of C-reactive protein, rheumatoid factor, alanine transaminase, aspartate transaminase and alkaline phosphatase in poly-arthritic rats. Moreover, the plant extract restored the immune organs' weight in treated rats. Treatment with P. harmala also significantly subdued the oxidative stress by reinstating superoxide dismutase, reduced glutathione, catalase and malondialdehyde in poly-arthritic rats. The plant extract notably restored the prostaglandin-E2 and tumor necrosis factor (TNF)-α in the serum of poly-arthritic rats., Conclusion: It was concluded that P. harmala extract had potential antioxidant, anti-inflammatory and antiarthritic activities, which primarily might be attributed to alkaloids, flavonoids and phenols., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The plant Berberis aristata is traditionally used and scientifically validated for treating obesity and hyperlipidemia. It is also traditionally used to treat gynecological abnormalities. Therefore, the present study was designed to evaluate the therapeutic potential of Berberis aristata for obesity-related reproductive changes and chemically characterize it., Methods: High-fat diet was given to 36 female rats for six weeks to induce obesity and infertility. These obese rats were treated with 10 mg/kg orlistat or the plant extract at 125-500 mg/kg for 45 days., Results: The GC-MS analysis of the plant extract included fructose, thymic acid and other hydrocarbons. The plant extract revealed a remarkable free radical scavenging activity. The treated animals exhibited a decrease in total cholesterol and triglycerides (p<0.001), insulin and leptin levels (p<0.05), visceral fat, and body weight while increasing the estradiol level at 500 mg/kg dose of the plant extract as compared with untreated animals as demonstrated from the histology of the ovary. Oxidative stress biomarkers such as superoxide dismutase, nitric oxide, malondialdehyde and reduced glutathione were significantly (p<0.01-0.001) ameliorated in treated rats., Conclusion: B. aristata exhibited substantial potential against obesity-inducedreproductive damage in female rats by reducing oxidative stress and resistance to leptin and insulin., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

To evaluate the anti-diabetic potential of aqueous methanolic extract of Conyza bonariensis amongst the Wistar rats. Phytochemical and High Performance Liquid Chromatography (HPLC) analyses of phenols and flavonoids were examined. The plant extract (250 and 500mg/kg/day) was explored for its anti-hyperglycemic effect for 14 days in normoglycemic and alloxan-induced diabetic rats using the oral glucose tolerance test (OGTT). HPLC analyses demonstrated the composition of the plant extract as gallic acid, cinnamic acid, quercetin, p-coumaric acid and syringic acid. The blood glucose concentrations in experimental diabetic as well as non-diabetic rats significantly decreased with doses 250 and 500 mg/kg in OGTT. Moreover, the significant drop in fasting glucose level was observed following 14 days of therapy. It also ameliorated the serum cholesterol, total protein, low and high density lipoproteins, glycosylated hemoglobin A1C and serum amylase with respect to untreated rats suffering from diabetes. There appeared to be no significant alteration with regard to body weight amongst the treated rats. The plant extract revamped the pancreatic islets of Langerhans and abridged alloxan-induced degenerative changes in the liver. It can be concluded that Conyza bonariensis extract has a pronounced hypoglycemic effect on diabetes due to the presence of phytochemicals.

In the current research, attempt is made to fabricate a nanoemulsion (NE) containing an antifungal agent. The prepared formulation has been expected to enhance skin penetration. It is also studied for in vitro drug release and toxicity assessment. Spontaneous titration method was used for preparation of NE. Prepared NE were characterized for their charge, size, morphology, rheological behaviour, drug release profile, skin permeability. The drug permeation and skin irritation were investigated. The in vitro antifungal activity was inspected using the well agar diffusion method. Miconazole NE showed good penetration in the skin as compared to marketed products. SEM showed semispherical shapes of the droplets. Zeta potential and zeta sizer showed that size was in nano ranges having positive charge., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Introduction: Resistant strains of bacteria are rapidly emerging with increasing inappropriate use of antibiotics rendering them less efficacious. Self-purchasing of antibiotics particularly for viral infections is a key driver of inappropriate use, especially in lower- and middle-income countries. There is a particular issue in countries such as Pakistan. Consequently, there is a need to assess current rates of self-purchasing especially for reserve antibiotics to guide future policies., Aims: Assess the extent of current antibiotic sales without a prescription in urban areas of Pakistan., Methodology: A multicenter cross-sectional study was conducted in different areas of Punjab, Pakistan using Simulated Client technique. The investigators demanded different predefined antibiotics from WHO AWaRe groups without prescription. Three levels of demand were used to convince the pharmacy staff in order to dispense the antibiotic without a prescription. A data collection form was completed by simulated clients within 15 min of each visit., Results: Overall 353 pharmacies and medical stores were visited out of which 96.9% pharmacies and medical stores dispensed antibiotics without demanding a prescription (82.7% at demand level 1 and 14.2% at demand level 2), with only 3.1% of pharmacies refusing to dispense antibiotics. The most frequently dispensed antibiotic was ciprofloxacin (22.1%). Surprisingly, even the reserve group antibiotics were also dispensed without a prescription. In only 25.2% visits, pharmacy staff guided patients about the use of antibiotics, and in only 11.0% pharmacists enquired about other medication history., Conclusion: Currently, antibiotics are easily acquired without a legitimate prescription in Pakistan. There is a need for strict adherence to regulations combined with a multi-dimensional approach to enhance appropriate dispensing of antibiotics and limit any dispensing of WHO restricted antibiotics without a prescription., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Fast dissolving orodispersible film (ODF) was prepared for concurrent administration of biopharmaceutical classification system (BCS) class II drugs, i.e., meloxicam (MX) and tizanidine (TZ), using natural (xanthan gum), semisynthetic (hydroxypropyl methylcellulose and hydroxyethyl cellulose) and synthetic (polyvinyl alcohol) polymers. Compatibility of the ingredients of ODFs was ascertained through Fourier transform infra-red spectroscopy and differential scanning calorimetry. ODFs were characterized through disintegration time, pH of the surface of film, tensile strength, folding endurance, % elongation and content uniformity (MX and TZ) which were found in the range between 17±1.3-56±3.1 s, 5.11±0.07-6.28±0.05, 14.721±1.2-33.084±3.1 N/m2, > 100, 3.33±0.53-10.04±0.77 % and 98.01-99.34 % (MX) and 97.48-99.03 % (TZ), respectively. The values of moisture uptake, moisture loss and loss on drying of all formulations were in the range from 1.06±0.09-7.51±0.93 %, 0.06±0.01-2.3±0.08 % and 0.008±0.002-0.03±0.03 %, respectively. In vitro drug release study in simulated saliva fluid of pH 7.4 has shown that > 90 % MX and TZ was released within 5 min. Visual inspection, scanning electron microscope and X-ray diffraction analysis of all ODFs expressed their smooth surfaces. ODF prepared from xanthan gum (F5) exhibited better physicochemical and mechanical properties as compared to other formulations.

Background: Guidelines assisted appropriate use of prophylactic antibiotics can lower the prevalence of surgical site infections (SSIs). The present study was conducted to evaluate the impact and cost-benefit value of pharmacist's educational intervention for antibiotic use in post-surgical prophylaxis., Methods: A prospective quasi experimental study was conducted by enrolling 450 patients from tertiary care hospital of Lahore, Pakistan, 225 patients in each, control and intervention, arm using non-random convenient sampling. The study parameters included antibiotic indication, choice, dose, frequency, duration and associated costs. This study is registered with Chinese Clinical Trial Registry # ChiCTR-OON-17013246., Results and Conclusion: After educational intervention, in post-intervention arm, total compliance in terms of correct antibiotic choice, dose, frequency and duration increased from 1.3% to 12.4%. The rate of inappropriate antibiotic choice did not change significantly. After intervention only metronidazole utilization decreased (16%) significantly (p=0.011). Significant reductions were observed in mean duration of antibiotic prophylaxis (17%, p=0.003), average number of prescribed antibiotics (9.1%, p=0.014) and average antibiotic cost (25.7%, p=0.03), with reduction in mean hospitalization cost (p=0.003) and length of stay (p=0.023). Educational intervention was significantly associated (OR; 2.4, p=0.005) with appropriate antibiotic prophylaxis. The benefit of pharmacist intervention, mean antibiotic cost savings to mean cost of pharmacist time, was 4.8:1. Thus, the educational intervention resulted in significant reductions in the duration and average number of antibiotic use having considerable effect on therapy and hospitalization cost., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The role of a pharmacist in primary health care settings of Pakistan is still obscure. Thus, we aimed to demonstrate the pharmacist-led improvements in glycemic, blood pressure and lipid controls in type 2 diabetes mellitus (T2DM) patients of Lahore, Pakistan., Methods: The first open label, randomized control trial conducted at a primary health care facility of Lahore, Pakistan by enrolling 244 uncontrolled type 2 diabetes (hemoglobin A1 c, (HbA1c); 10.85 ± 1.74) patients. The pharmacological intervention included identification of drug related problems, drug interactions, change in dose, frequency and therapy switches in collaboration with physician, while non-pharmacological intervention consisted of diet, lifestyle and behavior counseling. Outcome measures were glycemic (HbA1c), blood pressure and lipid controls., Results: In intra-group comparison, compared to control arm (C, n = 52), subjects in the intervention arm (I, n = 83) demonstrated significant differences in process outcome measures; baseline vs final, such as HbA1c (C; 10.3 ± 1.3 vs 9.7 ± 1.3, p <  0.001, I; 10.9 ± 1.7 vs 7.7 ± 0.9, p <  0.0001), systolic blood pressure (SBP) (C; 129.9 ± 13.9 vs 136 ± 7.1, p = 0.0001, I; 145 ± 20.4 vs 123.9 ± 9.9 mmHg, p <  0.0001), diastolic blood pressure (DBP) (C; + 4, p = 0.03, I; - 7 mmHg, p <  0.0001), cholesterol (C; 235.8 ± 57.7 vs 220.9 ± 53.2, p = 0.15, I; 224 ± 55.2 vs 153 ± 25.9 mg/dL, p < 0.0001), triglycerides (C; 213.2 ± 86.6 vs 172.4 ± 48.7, p = 0.001, I; 273 ± 119.4 vs 143 ± 31.6 mg/dL, p < 0.0001) and estimated glomerular filtration rate (eGFR) (C; 77.5 ± 18.6 vs 76 ± 14.2, p = 0.5, I; 69.4 ± 21.3 vs 93.8 ± 15.2 ml/min/1.73m 2 , p < 0.0001). Likewise, inter-group improvements were more significant in the subjects of intervention group at final follow up in comparison to control for various process outcome measures; HbA1c (p < 0.001), SBP (p < 0.0001), DBP (p = 0.02), cholesterol (p < 0.0001), triglycerides (p < 0.0001), SCr (p < 0.001), eGFR (p < 0.001). Moreover, both male and female subjects exhibited similar responses towards intervention with similar improvements in outcome measures., Conclusion: These data suggested that pharmacist intervention in collaboration with physician in primary health care settings may result in significant improvements in glycemic, blood pressure and lipid controls in Pakistani population., Trial Registration: The trial was registered retrospectively with International Standard Registered Clinical/soCial sTudy Number (ISRCTN) registry on July 26, 2017 under nutritional, metabolic, endocrine category with assigned registration # ISRCTN22657497 and can be assessed at https://doi.org/10.1186/ISRCTN22657497.

Medicinal plants are playing an imperative role in the therapy for treating various chronic ailments including arthritis. The present study was focused on finding in-vitro and in-vivo anti-arthritic potential of P. braunii roots. In vitro protein denaturation, membrane stabilization and anti-trypsinase assays were carried out to demonstrate anti-arthritic activity of the extracts. Furthermore, the extracts exerting promising in vitro anti-arthritic potential were tested orally at 150, 300 and 600mg/kg/day against formaldehyde induced arthritis in Wistar rats. The methanolic, aqueous and ethyl acetate extracts of the plant revealed noteworthy in vitro anti-arthritic activities while mitigating formaldehyde induced paw edema in dose dependent manner. Methanolic and aqueous extracts showed the highest inhibition (p<0.05) of paw edema, arthritic indices, reduced elevated level of platelets and leukocytes while increasing hemoglobin and body weight of arthritic rats. Anti-arthritic activity of the plant extracts may be due to inhibition of protein denaturation and lysosomal membrane stabilization. The plant exhibited good anti-arthritic potential.

A simple, rapid and accurate reverse phase high performance liquid chromatographic (RP- HPLC) method was developed for the quantification of lornoxicam in oral disintegrating tablets (ODTs) and in rabbit's plasma. C18 Hypersil™ column was used as stationary phase to separate the drug. Mobile phase methanol: acetonitrile: water (60:30:10) was run isocratically at flow rate of 1 mL/min at room temperature. Mean retention time was 4.23 minutes and minimum amount of lornoxicam that can be measured was 7 ng/mL in rabbit's plasma. Good linearity was observed in concentration range of 10-100 ng/mL with regression coefficient R2 value of 0.9989 and slope value 23773. As per ICH norms, developed method was validated in terms of interday, intraday precision, accuracy, specificity, limit of detection (LOD), limit of quantification (LOQ) and drug plasma stability studies. All the data obtained revealed that this method can be used for in-vitro and in-vivo determination of lornoxicam in various pharmaceutical preparations.

We write to report a rare case of unilateral cancer-associated retinopathy previously undocumented in the literature. Cancer-associated retinopathy is an uncommon paraneoplastic syndrome. It is characterised by retinal antigen autoantibodies causing rod and cone dysfunction and abnormal electroretinography findings with consequent progressive visual loss.Our patient, known to have a primary cervical intraepithelial neoplasia, presented with unilateral blurred vision as well as a disturbance in colour and night vision. Electroretinography findings of reduced a and b waves in the right eye, together with a fundoscopic appearance of a mottled retinal pigment epithelium, attenuated blood vessels and optic disc pallor were consistent with unilateral cancer-associated retinopathy. Posterior subtenon injections of triamcinolone were administered to control active disease. With periocular steroid injections, at 4 years, our patient's visual acuity remained relatively stable and her condition persisted strictly unilaterally. Cancer-associated retinopathy may be the first presenting sign of an underlying malignancy or may indicate its recurrence. Moreover, in patients with a diagnosed gynaecological malignancy, visual symptoms could reflect cancer-associated retinopathy. In our patient visual symptoms came secondary to the diagnosis of cancer., (© The Author(s) 2015.)

Purpose: The aim of this work is to demonstrate a new image processing technique that can provide a "near real-time" 3D reconstruction of the articular cartilage of the human knee from MR images which is user friendly. This would serve as a point-of-care 3D visualization tool which would benefit a consultant radiologist in the visualization of the human articular cartilage., Methods: The authors introduce a novel fusion of an adaptation of the contour method known as "contour interpolation (CI)" with radial basis functions (RBFs) which they describe as "CI-RBFs." The authors also present a spline boundary correction which further enhances volume estimation of the method. A subject cohort consisting of 17 right nonpathological knees (ten female and seven male) is assessed to validate the quality of the proposed method. The authors demonstrate how the CI-RBF method dramatically reduces the number of data points required for fitting an implicit surface to the entire cartilage, thus, significantly improving the speed of reconstruction over the comparable RBF reconstruction method of Carr. The authors compare the CI-RBF method volume estimation to a typical commercial package (3d doctor), Carr's RBF method, and a benchmark manual method for the reconstruction of the femoral, tibial, and patellar cartilages., Results: The authors demonstrate how the CI-RBF method significantly reduces the number of data points (p-value < 0.0001) required for fitting an implicit surface to the cartilage, by 48%, 31%, and 44% for the patellar, tibial, and femoral cartilages, respectively. Thus, significantly improving the speed of reconstruction (p-value < 0.0001) by 39%, 40%, and 44% for the patellar, tibial, and femoral cartilages over the comparable RBF model of Carr providing a near real-time reconstruction of 6.49, 8.88, and 9.43 min for the patellar, tibial, and femoral cartilages, respectively. In addition, it is demonstrated how the CI-RBF method matches the volume estimation of a typical commercial package (3d doctor), Carr's RBF method, and a benchmark manual method for the reconstruction of the femoral, tibial, and patellar cartilages. Furthermore, the performance of the segmentation method used for the extraction of the femoral, tibial, and patellar cartilages is assessed with a Dice similarity coefficient, sensitivity, and specificity measure providing high agreement to manual segmentation., Conclusions: The CI-RBF method provides a fast, accurate, and robust 3D model reconstruction that matches Carr's RBF method, 3d doctor, and a manual benchmark method in accuracy and significantly improves upon Carr's RBF method in data requirement and computational speed. In addition, the visualization tool has been designed to quickly segment MR images requiring only four mouse clicks per MR image slice.

Current study was conducted to investigate antimicrobial activity of fruit extracts of two Solanaceous plants (Solanum nigrum and Solanum xanthocarpum) found in Pakistan. Petroleum ether, chloroform, dichloromethane, ethyl acetate, acetone, methanol and water were utilized for extraction. The highest percentages of polar components of both the species were extracted by water; little amount of non-polar components by petroleum ether while very low quantities by other solvents. Antimicrobial activities were estimated by measuring zones of inhibition through hole-plate diffusion method, against three species of Gram positive bacteria, five species of Gram negative bacteria and three species of fungi selected for this study. Doses of 5, 10 and 15 mg/mL prepared through methanolic extracts of each plant's powdered fruit material displayed significant zones of inhibition against all three Gram positive bacteria, three of the Gram negative bacteria out of five and against all three fungi. Although these doses exhibited significant zones of inhibition but they are not as potent as standards: ampicillin or amphotericin B. The present study assures the possible potential of antimicrobial as well as antifungal activity of fruit extracts of these plants.

This study was aimed to determine effects of penetration enhancers and plasticizers on drug release from rationally designed formulations of flurbiprofen based transdermal drug delivery system. Matrix type transdermal patches were formulated with ethyl cellulose (EC) as a polymer by using plate casting method. The plasticizers such as propylene glycol (PG) and dibutyl phthalate (DBP), and enhancers such as Span 20, Tween 20, sodium lauryl sulfate (SLS), isopropyl myristate (IPM) and ethanol (EtOH) were formulated in different concentrations in the patches. Such different combinations of polymer with various enhancers and plasticizers in patches were evaluated for their effect on the physicochemical properties and drug release behavior of flurbiprofen. The drug release study was carried out by the paddle-over-disk method and permeation of drug was performed by Franz diffusion cell using rabbit skin. Patches having ethanol with ethyl cellulose showed more uniformity in the physical properties while the smoothness and clarity of patches containing sodium lauryl sulfate were not satisfactory. The drug release from patches followed Higuchi and Korsmeyer-Pappas model while maximum drug release was obtained by isopropyl myristate (903 microg). It was concluded that the patches having ethyl cellulose with isopropyl myristate and propylene glycol are more useful for transdermal patches of flurbiprofen.

In this article, we propose a novel method for the fast 3D reconstruction of real osteoarthritic (OA) holes in a human femoral cartilage. Initially, semi-automated Region-Based Segmentation (region-growing) and Bounding Box techniques are used to extract femoral cartilage slices from MRI scans of the knee. OA holes were detected and filled automatically by our contour interpolation/RBF (CI-RBF) method and 3D models of both the femoral cartilage and OA holes were reconstructed separately. The method was then applied to a single human knee and results proved it fast, reliable and accurate for reconstructing a 3D model of the femoral cartilage from MRI images with an extremely low root mean square error of 1.67% in the estimated volume of the automatically filled to the manually filled femoral cartilage slices. As per authors' knowledge this is the first time real OA hole has automatically been identified and filled.

Gliclazide is an oral hypoglycemic agent, indicated in non insulin dependent diabetes mellitus and in patients with diabetic retinopathy. It has good tolerability and is a short acting sulfonyl urea that requires large dose to maintain the blood glucose level. So development of a sustained release formulation of gliclazide (GLZ) is required for better patient compliance. This study was conducted to assess the effects of different drug polymer ratios on the release profile of gliclazide from the matrix. Oral matrix tablets of gliclazide were prepared by hot melt method, using pure and blended mixture of glyceryl monostearate (GMS) and stearic acid (SA) in different ratios. In vitro release pattern was studied for 8 h in phosphate buffer media (pH 7.4). Different kinetic models including zero order, first order, Higuchi and Peppas were applied to evaluate drug release behavior. Drug excipient compatibility was evaluated by scanning with DSC and FTIR. Higuchi model was found the most appropriate model for describing the release profile of GLZ and non-Fickian release was found predominant mechanism of drug release. The release of drug from the matrix was greatly controlled by GMS while SA appeared to facilitate the release of drug from matrix tablets. FTIR results showed no chemical interaction between drug and the polymers, and DSC results indicated amorphous state of GLZ and polymers without significant complex formation. The results indicate that matrix tablets of gliclazide using glyceryl monostearate and stearic acid showed marked sustained release properties.

In this article, we propose a new method for the fast 3D reconstruction of simulated osteoarthritic holes in a human patella. Initially, clean patella slices were extracted from MRI scans of the knee using Region-Based Segmentation (region-growing) and Bounding Box techniques. Osteoarthritic (OA) holes were then simulated in the patella slices. Our contour interpolation/RBF (CI/RBF) method was then used to detect the hole automatically and reconstruct 3D models of both the patella and OA hole separately. The method presented here proves fast, reliable and efficient for reconstructing a 3D model of the patella from MRI images with an extremely low error of 0.33%.

Sixty-seven pyrimidine nucleobase analogues were evaluated as ligands of Toxoplasma gondii orotate phosphoribosyltransferase (OPRTase, EC 2.4.2.10) by measuring their ability to inhibit this enzyme in vitro. Apparent Ki values were determined for compounds that inhibited T. gondii OPRTase by greater than 20% at a concentration of 400 microM. 1-Deazaorotic acid (0.47 microM) and 5-azaorotic acid (2.1 microM) were found to bind better (8.3- and 1.9-fold, respectively) to T. gondii OPRTase than orotic acid, the natural substrate of the enzyme. Based on these results, a structure-activity relationship of ligand binding to OPRTase was formulated using uracil, barbituric acid, and orotic acid as reference compounds. It was concluded that the following structural features of pyrimidine nucleobase analogues were required or strongly preferred for binding: (i) an endocyclic pyridine-type nitrogen or methine at the 1-position; (ii) exocyclic oxo groups at the 2- and 4-positions; (iii) a protonated endocyclic pyridine-type nitrogen at the 3-position; (iv) an endocyclic pyridine-type nitrogen or methine at the 5-position; (v) an exocyclic hydrogen or fluorine at the 5-position; (vi) an endocyclic pyridine-type nitrogen or methine at the 6-position; and (vii) an exocyclic negatively charged or electron-withdrawing group at the 6-position. A comparison of the results from the present study with those from a previous study on mammalian OPRTase [Niedzwicki et al., Biochem Pharmacol 33: 2383-2395, 1984] identified four compounds (6-chlorouracil, 5-azaorotic acid, 1-deazaorotic acid, and 6-iodouracil) that may bind selectively to T. gondii OPRTase.