Amelioration of tableting properties and dissolution rate of naproxen co-grinded with nicotinamide: preparation and characterization of co-grinded mixture.

OBJECTIVE AND SIGNIFICANCE: Reducing the dimensions, when other additives are present, shows potential as a method to improve the dissolution and solubility of biopharmaceutical classification system class II drugs that have poor solubility. In this investigation, the process involved grinding naproxen with nicotinamide with the aim of improving solubility and the rate of dissolution. METHODS: Naproxen was subjected to co-milling with urea, dimethylurea, and nicotinamide using a planetary ball mill for a duration of 90 min, maintaining a 1:1 molar ratio for the excipients (screening studies). The co-milled combinations, naproxen in its pure milled form, and a physical mixture were subjected to analysis using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), and solubility assessment. The mixture displaying the highest solubility (naproxen-nicotinamide) was chosen for further investigation, involving testing for intrinsic dissolution rate (IDR) and Fourier-transform infrared spectroscopy (FTIR) after co-milling for both 90 and 480 min. RESULTS AND CONCLUSION: The co-milled combination, denoted as S-3b and consisting of the most substantial ratio of nicotinamide to naproxen at 1:3, subjected to 480 min of milling, exhibited a remarkable 45-fold increase in solubility and a 9-fold increase in IDR. XRPD analysis of the co-milled samples demonstrated no amorphization, while SEM images portrayed the aggregates of naproxen with nicotinamide. FTIR outcomes negate the presence of any chemical interactions between the components. The co-milled sample exhibiting the highest solubility and IDR was used to create a tablet, which was then subjected to comprehensive evaluation for standard attributes. The results revealed improved compressibility and dissolution properties.

New Acetamide-Sulfonamide-Containing Scaffolds: Antiurease Activity Screening, Structure-Activity Relationship, Kinetics Mechanism, Molecular Docking, and MD Simulation Studies.

The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a result, drug conjugates are an active area of research and development in medicinal chemistry. This research demonstrates acetamide-sulfonamide scaffold preparation after conjugation of ibuprofen and flurbiprofen with sulfa drugs, and these scaffolds were then screened for urease inhibition. The newly designed conjugates were confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and elemental analysis. Ibuprofen conjugated with sulfathiazole, flurbiprofen conjugated with sulfadiazine, and sulfamethoxazole were found to be potent and demonstrated a competitive mode of urease inhibition, with IC50 (µM) values of 9.95 ± 0.14, 16.74 ± 0.23, and 13.39 ± 0.11, respectively, and urease inhibition of 90.6, 84.1, and 86.1% respectively. Ibuprofen conjugated with sulfanilamide, sulfamerazine, and sulfacetamide, whereas flurbiprofen conjugated with sulfamerazine, and sulfacetamide exhibited a mixed mode of urease inhibition. Moreover, through molecular docking experiments, the urease receptor-binding mechanisms of competitive inhibitors were anticipated, and stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and that no conformational changes occurred during the simulation. The findings demonstrate that conjugates of approved therapeutic molecules may result in the development of novel classes of pharmacological agents for the treatment of various pathological conditions involving the urease enzyme.

Exposure Assessment of Essential and Potentially Toxic Metals in Wheat-Based Sweets for Human Consumption: Multivariate Analysis and Risk Evaluation Studies.

In recent years, there has been a growing concern about the negative impact of unforeseen contaminants such as metals in commonly consumed food items, which pose a threat to human well-being. Therefore, it is of utmost importance to evaluate the levels of these contaminants to guarantee the safe consumption of these food items. The goal of the current research is to determine the levels of essential (EMs: Mg, Ca, Mn, Fe, Co, Cu, and Zn) and potentially toxic metals (PTMs: Al, Cr, Ni, As, Cd, and Pb) in various brands of wheat-based sweets. One hundred samples were collected and analysed via flame atomic absorption spectrometry (FAAS) and inductively coupled plasma-optical emission spectrometry (ICP-OES). Also, the current study was to investigate the distribution, correlation, and multivariate analysis of 13 metals (Mg, Ca, Mn, Fe, Co, Cu, Zn, Al, Cr, Ni, As, Cd, and Pb). Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used to interpret the metals' association. The concentration (mg/kg) ranges of EMs were, in order, Mg (12.70-65.67), Ca (24.02-209.12), Mn (1.32-9.61), Fe (4.55-111.23), Co (0.32-8.94), Cu (2.12-8.61), and Zn (2.60-19.36), while the concentration (mg/kg) ranges of PTMs were, in order, Al (0.32-0.87), Cr (0.17-5.74), Ni (0.36-1.54), Cd (0.16-0.56), and Pb (0.14-0.92), and As was not detected in any sample under investigation. The HCA data revealed that Co, Al, and Ni form clusters with other metals. Sweets are prepared at high temperatures, and the elevated temperatures can increase the likelihood of Ni and Al leaching from stainless steel. Tolerable dietary intake (TDI) values for Ni were higher than the values established by the European Food Safety Authority (EFSA). The CR value found for the Ni and Cr was at the threshold level of cancer risk, if an amount of 25 g were to be used over a lifetime. In a nutshell, this study highlights the monitoring of EM and PTM levels in wheat-based sweets, and from a food safety perspective, the study is important for consumers of wheat-based sweets.

Assessment of potentially toxic metal(loid)s contamination in soil near the industrial landfill and impact on human health: an evaluation of risk.

The generation of solid waste is increasing with each passing day due to rapid urbanization and industrialization and has become a matter of concern for the international community. Leachate leakages from landfills pollute the soil and can potentially harm the human health. In this paper, inductively coupled plasma-optical emission spectrometric studies were employed to assess and analyze the composition of metals (Ba, Cd, Pb, Hg, Cu, Cr and Mn) and metalloid (As) in soil samples. Results of Cr, Mn, Cu, As, Ba, Cd, Pb and Hg from CRM (certified reference material, SRM 2709a) of San Joaquin soil were evaluated and reported in terms of percent recoveries which were in the range of 97.6-102.9% and show outstanding extraction efficiency. Other than copper, where the permitted limit set by the EU is specified as 50-140 mg/kg in soil, the average amount of all the metals in soil was found within the permissible limits provided by WHO, the European Community (EU) and US EPA. Soil contaminated with Hg (PERI = 100) and Cd (PERI = 145.50) posed an ecological risk significantly. Pollution load index (PLI) value is greater than 1, while degree of contamination (Cdeg) value is less than 32 which indicated that the soil is polluted and considerably contaminated with metals and metalloid, respectively. In terms of the average daily dosage (ADD) of soil, children received the highest doses of all metals (ADDing = 1.315 × 10-7 - 2.470 × 10-3 and ADDderm = 9.939 × 10-7 - 5.292 × 10-11), whereas ADDing (1.409 × 10-8 - 2.646 × 10-4) was found greater in adults. For all metals except for Ba, the hazard quotient (HQ) trend in both children and adults was observed to be HQing > HQderm > HQinh of soil. Children who are at the lower edge of cancer risk had a lifetime cancer risk (LCR) of 2.039 × 10-4 for Cr from various paths of soil exposure.

Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil.

A targeted delivery system is primarily intended to carry a potent anticancer drug to specific tumor sites within the bodily tissues. In the present study, a carrier system has been designed using folic acid (FA), bis-amine polyethylene glycol (PEG), and an anticancer drug, 5-fluorouracil (5-FU). FA and PEG were joined via an amide bond, and the resulting FA-PEG-NH2 was coupled to 5-FU producing folate-polyethylene glycol conjugated 5-fluorouracil (FA-PEG-5-FU). Spectroscopic techniques (UV-Vis, 1HNMR, FTIR, and HPLC) were used for the characterization of products. Prodrug (FA-PEG-5-FU) was analyzed for drug release profile (in vitro) up to 10 days and compared to a standard anticancer drug (5-FU). Folate conjugate was also analyzed to study its folate receptors (FR) mediated transport and in vitro cytotoxicity assays using HeLa cancer cells/Vero cells, respectively, and antitumor activity in tumor-bearing mice models. Folate conjugate showed steady drug release patterns and improved uptake in the HeLa cancer cells than Vero cells. Folate conjugate treated mice group showed smaller tumor volumes; specifically after the 15th day post-treatment, tumor sizes were decreased significantly compared to the standard drug group (5-FU). Molecular docking findings demonstrated importance of Trp138, Trp140, and Lys136 in the stabilization of flexible loop flanking the active site. The folic acid conjugated probe has shown the potential of targeted drug delivery and sustained release of anticancer drug to tumor lesions with intact antitumor efficacy.

Hepatocellular Carcinoma (HCC), Where do we stand? Current situation.

OBJECTIVE: To identify the stage of Hepatocellular Carcinoma (HCC) at the time of presentation. METHODS: This cross sectional observational prospective study was carried out at Gastro Department of Combined Military Hospital (CMH) Multan from August 2017 to December 2018. Patients were diagnosed on the basis of alpha fetoprotein, abdominal ultrasound, triphasic contrast enhanced computerized tomography (CECT). They were evaluated for etiology including Hepatitis B, C and non B & C. The patients were inquired about the previous treatment and when they came to know about the HCC. Staging of the tumor was done on the basis BCLC (Barcelona cancer liver clinic) and Melan's criteria. Performance status (PS) of the patient was checked by Eastern Cooperative Oncology Group (ECOG) criteria. Severity of cirrhosis was assessed by CTP (Child Turcotte Pugh) and Model for end stage liver disease (MELD) score. The data was analyzed in IBM SPSS version 22. RESULTS: Out of 135 patients 78% were males and 22% females. Age Mean SD was 58.81± 9.366. Frequency of hepatitis C, B, combined B, C and non-B non-C was 80%, 11%, 2.8% and 6.2% respectively. 96(73.8%) never got the treatment before for Hepatitis. 81(62.3%) came to know first time on this index admission. Maximum numbers of patients were in BCLC stage B i.e. 82(55.2%) with ECOG grade of one i.e.57 (39.3%), at the time of presentation. Mean MELD and CTP score were 12.24, 7.34 (class B) respectively. CONCLUSION: HCV was the most common in HCC, never treated before, presented for the first time in advance stage of the disease where very limited treatment options left behind.

Extraction, formulation and characterization of an in vitro and ex-vivo evaluation of Thymus serpyllum L. (Thymus oil) from topical preparations using dialysis cellulose membrane and natural rabbit skin.

Herbal remedies like the Thymus serpyllum L. is useful in traditional medicine for the treatment of many diseases especially congestion, and bronchitis. The purpose of this study was to formulate a micro-emulsion, a gel and an ointment containing the plant hydro distilled thymus oil extracted from Thymus serpyllum L. collected from Ziarat, Balochistan. The prepared formulations were subjected to in-vitro and ex vivo study release, High performance Liquid Chromatography (HPLC), Thin Layer Chromatography (TLC), to justify their suitability for topical use. The in-vitro and ex-Vivo release was studied using Franz Cells and using two different kinds of membrane synthetic dialysis cellulose membrane and natural rabbit skin and the amount of drug released was determined by HPLC at λ 274nm. The three formulations result obtained through dialysis cellulose membrane showed the faster release than the natural rabbit skin. However, the micro-emulsion, gel formulation showed the same release except ointment. The release from the above mentioned formulation can be arranged in the following descending order. micro-emulsion > Gel > Ointment. The best fit of release kinetics was achieved by Krosmeyer- Peppas, the TLC and HPLC identifies the Thymol, isolation and quantification of the marker. This study demonstrates that it is necessary to assess the impact of release and permeability pattern of different formulations. In vitro and ex-vivo diffusion cell experiments can be utilized to develop formulations of traditional medicines identifies.

Formulation, characterization and in vivo evaluation of Hedera helix L., topical dosage forms.

The purpose of this study was to prepare topical formulations of micro emulsion, gel and ointment containing the Hedera helix L. extracts against asthma and to evaluate the physicochemical characteristics. A validated HPLC method was used for the analysis of blood plasma. In-vivo studies of the drugs were compared in rabbit plasma with oral dosing. Stability studies were performed for 3 months. The results showed that formulations were stable. No Skin irritation observed on rabbits. The optimized micro emulsion and gel showed fast absorption. Maximal plasma concentration (cmax) and the maximal time to reach cmax (tmax) were 70.226µg/mL, 75.26µg/mL and 2 hours for the micro emulsion and gel, 90.11µg/mL and 1 hour for the oral drug syrup respectively. Pharmacokinetic parameters such as tmax, cmax and AUC of the selected formulations and oral dosing were significantly different (P < 0.01).

Sulfonamides containing curcumin scaffold: Synthesis, characterization, carbonic anhydrase inhibition and molecular docking studies.

Curcumin is a multi-functional pharmacologically safe natural agent with proven cytoprotective effects to healthy human cells. In this study, a new series of sulfonamides with curcumin scaffold were synthesized, characterized and investigated for their carbonic anhydrase isoenzyme I (human) and II (bovine) isoforms. The structures of newly synthesized compounds were described by IR, 1H NMR and 13C NMR spectral data. Compound 14 showed the Ki value of 0.99 µM with highest inhibitory activity among all other synthesized compounds against hCA-I enzyme. Similarly enzyme kinetic studies of compound 14, 16 and 30 against bCAII enzyme showed Ki values of 0.71, 0.67 and 0.71 µM respectively. Our biological assays results showed that most of active compounds have similar inhibitory activities compared to standard acetazolamide drug. The molecular docking predicted binding modes showed that these compounds bind with hCA-1 enzyme in similar fashion.

Investigations of Structural Requirements for BRD4 Inhibitors through Ligand- and Structure-Based 3D QSAR Approaches.

The bromodomain containing protein 4 (BRD4) recognizes acetylated histone proteins and plays numerous roles in the progression of a wide range of cancers, due to which it is under intense investigation as a novel anti-cancer drug target. In the present study, we performed three-dimensional quantitative structure activity relationship (3D-QSAR) molecular modeling on a series of 60 inhibitors of BRD4 protein using ligand- and structure-based alignment and different partial charges assignment methods by employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches. The developed models were validated using various statistical methods, including non-cross validated correlation coefficient (r²), leave-one-out (LOO) cross validated correlation coefficient (q²), bootstrapping, and Fisher's randomization test. The highly reliable and predictive CoMFA (q² = 0.569, r² = 0.979) and CoMSIA (q² = 0.500, r² = 0.982) models were obtained from a structure-based 3D-QSAR approach using Merck molecular force field (MMFF94). The best models demonstrate that electrostatic and steric fields play an important role in the biological activities of these compounds. Hence, based on the contour maps information, new compounds were designed, and their binding modes were elucidated in BRD4 protein's active site. Further, the activities and physicochemical properties of the designed molecules were also predicted using the best 3D-QSAR models. We believe that predicted models will help us to understand the structural requirements of BRD4 protein inhibitors that belong to quinolinone and quinazolinone classes for the designing of better active compounds.

Azomethines, isoxazole, N-substituted pyrazoles and pyrimidine containing curcumin derivatives: Urease inhibition and molecular modeling studies.

Curcumin has shown large number of pharmacological properties against different phenotypes of various disease models. Different synthetic routes have been employed to develop its various derivatives for diverse biological functions. In this study, curcumin derived azomethine, isoxazole, pyrimidines and N-substituted pyrazoles were synthesized to investigate their urease enzyme inhibition. The structures of newly synthesized compounds were described by IR, MS, 1H NMR and 13C NMR spectral data. Urease enzyme inhibition was evaluated through in vitro assays in which compound 8b was found to be the most potent (IC50 = 2.44 ± 0.07 µM) among the tested compounds. The compounds with diazine ring system except the 4d showed better urease inhibition (IC50 = 11.43 ± 0.21-19.63 ± 0.28 µM) than the standard urease inhibitor thiourea (IC50 = 22.61 ± 0.23 µM). Similarly enzyme kinetics data revealed that compounds 3c-3e and 8b were competitive inhibitors with Ki values of 20.0, 19.87, 20.23 and 19.11 µM respectively while the compounds 4b, 4c and 4e were mixed type of inhibitors with Ki values 6.72, 19.69 and 6.72 µM respectively. Molecular docking studies were also performed to identify the plausible binding modes of the most active compounds.

Stability Indicating UHPLC-PDA Assay for Simultaneous Determination of Antazoline Hydrochloride and Naphazoline Hydrochloride in Ophthalmic Formulations.

In the present study, a newly developed method based on ultrahigh performance liquid chromatography (UHPLC) was optimized for the simultaneous determination of antazoline hydrochloride (ANZ) and naphazoline hydrochloride (NFZ) in ophthalmic formulations. Isocratic separation of ANZ and NFZ was performed at 40 °C with an ACE Excel 2 C18-PFP column (2 µm, 2.1 × 100 mm) at a flow rate of 0.6 mL min-1 whereas the mobile phase consisted of acetonitrile/phosphate buffer (60:40, v/v, pH 3.0) containing 0.5% triethylamine. Both analytes were detected at a wavelength of 285 nm and the injection volume was 1.0 µL. The overall run time per sample was 4.5 min with retention time of 0.92 and 1.86 min for NFZ and ANZ, respectively. The calibration curve was linear from 0.500-100 µg mL-1 for ANZ and NFZ with a correlation coefficient ≥ 0.9981 while repeatability and reproducibility (expressed as relative standard deviation) were lower than 1.28 and 2.14%, respectively. In comparison with high-performance liquid chromatography (HPLC), the developed UHPLC method had remarkable advantages over HPLC as the run time was significantly reduced by 3.4-fold with a 5-fold decreased solvent consumption. Forced degradation studies indicated a complete separation of the analytes in the presence of their degradation products providing high degree of method specificity. The proposed UHPLC method was demonstrated to be simple and rapid for the determination of ANZ and NFZ in commercially available ophthalmic formulations providing recoveries between 99.6 and 100.4%.

Synthesis, antibacterial and antifungal possession of amino acids containing sulfonamide moieties.

Sulfonamides were developed by the simple reaction of amino acid with p-toluenesulfonyl chloride and structures of the new products (2a, 2b and 2c) were confirmed by elemental and spectral analysis (FT-IR, 1HNMR and13CNMR). In vitro, developed compounds were screened for their antibacterial and antifungal activities against two sensitive bacteria belonging to both gram positive and gram-negative types and two fungi. The synthesized sulfonamides (2a, 2b, 2c) exhibited excellent antifungal activities against the tested fungi. Among the tested compounds 2a and 2b have marked activity against E. coli with zone of inhibition (mm) 22.3±0.11and 20.2±0.26 (MIC: 12.5µg/mL, 12.5µg/mL) and S. aureus with zone of inhibition (mm) 20.2±0.26 and 23.2±0.55 (MIC: 12.5µg/mL, 6.25µg/mL). Compound 2c is moderately efficient towards E. coli (zone of inhibition (mm) 14.2±0.64, MIC: 100µg/mL) and no activity against S. aureus.

Synthesis, antimicrobial and antifungal possessions of tramadol esters: In vitro studies.

Tramadol esters were prepared by refluxing equimolar concentration of tramadol with leucine and asparagine separately with methanol, sulphuric acid and phthalic anhydride for 10 hours and temperature was maintained at 75°C. After refluxing, the colour of sample solutions were changed from colorless to yellow, blank solution was prepared in the same way as the sample solution except the Tramadol. Both the products and blank were neutralized with sodium carbonate and excess of sodium bicarbonate was precipitated as sodium sulphate, which was washed with acetone. The structures of both the products were confirmed with spectral data (FT-IR, 1HNMR and 13CNMR). Antimicrobial and anti-fungal property of derivative of analgesic tramadol drug was tested with one fungus and three sensitive bacteria belonging to both gram positive and gram-negative types. Esterified product of tramadol with leucine and asparagine showed moderate activity against Escherichia coli and Tricophyton rubrum. Both the products showed marked activity against Staphylococcus aureus and found no activity against Salmonella spp.

Improved limit of detection and quantitation development and validation procedure for quantification of zinc in Insulin by atomic absorption spectrometry.

A simple and expeditious analytical method for determination of zinc in human insulin isophane suspension by flame atomic absorption spectrophotometer (FAAS) was validated. The method was carried out on atomic absorption spectrometer with 0.4 nm bandwidth, 1.0 filter factor on deuterium (D2) background correction. The integration time was set at 3.0 second with 5.0 mA lamp current. The parameters of method validation showed adequate linearity, efficiency and relative standard deviation values were between 0.64%-1.69% (n=7), 1.31%-1.58% (n=10) for repeatability and intermediate precision respectively. The limit of detection 0.0032 µg/mL, 0.0173 µg/mL, 0.0231 µg/mL and limit of quantitation 0.0107µg/mL, 0.0578 µg/mL, 0.0694 µg/mL based on signal to noise (SN), calibration curve method (CCM) and fortification of blank (FB) were obtained respectively. The percentages of recovery for low, medium and high spiked concentration levels of zinc in human insulin were 99.38 ± 0.04 to 100.3 ± 0.03, 98.45 ± 0.38 to 100.3 ± 0.07 and 99.42 ± 0.03 to 99.42 ± 0.08 respectively. With the use of this method, five samples from each vial of human insulin isophane suspension were analyzed and the zinc content was determined. The zinc content were 22.1 ± 0.025 µg/mL and 24.3 ± 0.028 µg/mL which compliance the British Pharmacopoeia standard.

Expressional changes in growth and inflammatory mediators during Achilles tendon repair in diabetic rats: new insights into a possible basis for compromised healing.

Dysregulation of growth and inflammatory mediators might contribute to defective tissue homeostasis and healing, as commonly observed in sedentary lifestyles and in conditions such as diabetes mellitus type-2. The present study aims to assess expression changes in growth and inflammatory mediators in the intact and healing Achilles tendon of type-2 diabetic rats. The study utilized 11 male diabetic Goto-Kakizaki (GK) and 10 age- and sex-matched Wistar control rats. The right Achilles tendon was transected in all animals, whereas the left Achilles tendon remained intact. At 2 weeks post-injury, intact and injured tendons were assessed for gene expression for VEGF, Tß-4, TGF-ß1, IGF-1, COX-2, iNOS, HIF-1α, and IL-1ß by quantitative reverse transcription plus the polymerase chain reaction, and their protein distribution was studied by immunolocalization. In injured tendons of diabetic GK rats, VEGF and Tß-4 mRNA and corresponding protein levels were significantly down-regulated compared with those of injured Wistar controls. Compared with intact tendons of diabetic GK rats, TGF-ß1, IGF-1, and COX-2 RNA levels were higher, whereas iNOS mRNA levels were lower in injured tendons of diabetic GK rats. Within Wistar controls, healing at 2 weeks post-injury led to significantly down-regulated VEGF and iNOS mRNA levels in injured tendons, whereas TGF-ß1 and HIF-1α mRNA levels increased compared with intact tendons. Thus, dysregulation of inflammatory and growth mediators occurs in type-2 diabetes injured tendons. Our data suggest that therapeutic modulation of Tß-4 and VEGF represent a new regenerative approach in operated, injured, or degenerative tendon diseases in diabetes.

Determination of suitable microspore stage and callus induction from anthers of kenaf (Hibiscus cannabinus L.).

Kenaf (Hibiscus cannabinus L.) is one of the important species of Hibiscus cultivated for fiber. Availability of homozygous parent lines is prerequisite to the use of the heterosis effect reproducible in hybrid breeding. The production of haploid plants by anther culture followed by chromosome doubling can be achieved in short period compared with inbred lines by conventional method that requires self pollination of parent material. In this research, the effects of the microspore developmental stage, time of flower collection, various pretreatments, different combinations of hormones, and culture condition on anther culture of KB6 variety of Kenaf were studied. Young flower buds with immature anthers at the appropriate stage of microspore development were sterilized and the anthers were carefully dissected from the flower buds and subjected to various pretreatments and different combinations of hormones like NAA, 2,4-D, Kinetin, BAP, and TDZ to induce callus. The best microspore development stage of the flower buds was about 6-8 mm long collected 1-2 weeks after flower initiation. At that stage, the microspores were at the uninucleate stage which was suitable for culture. The best callus induction frequency was 90% in the optimized semisolid MS medium fortified with 3.0 mg/L BAP + 3.0 mg/L NAA.

Effect of teriparatide on bone regenerate after distraction osteogenesis.

OBJECTIVE: To determine the effect of teriparatide on new bone formation in a rat model of distraction osteogenesis. METHODS: The experimental study was conducted at the Aga Khan University Hospital, Karachi, in November-December 2010, and comprised male Sprague-Dawley rats weighing 250gm each who were allocated to two treatment groups, teriparatide and saline, both given subcutaneously for 7 weeks. Femoral distraction was done for 3 weeks at the rate of 0.4mm/day, followed by a further 4 weeks for consolidation. New bone formation was assessed using X-ray scoring system, bone densitometry and histology. RESULTS: The 12 rats in the study were divided into two groups of 6(50%) each. All rats in the teriparatide group showed new bone formation whereas bone formation was present only in 2(33.3%) rats in the saline group. Bone densitometry showed that area (size) of the new bone formed adjacent to the margins of the osteotomy site as well as the total bone mineral content of the new bone was significantly higher (p<0.05) in the teriparatide group. Histological analysis showed larger but statistically insignificant (p>0.05) area of woven and trabecular new bone in the teriparatide group. CONCLUSIONS: The results suggested a promising role of parathyroid analogue therapy in distraction osteogenesis for promoting bone formation and consolidation. This may have strong clinical implications in cases of limb lengthening and bone transport.

Development of Plumeria alba extract supplemented biodegradable films containing chitosan and cellulose derived from bagasse and corn cob waste for antimicrobial food packaging.

With the increase in global plastic pollution due to conventional plastic packaging (petroleum-derived), bioplastics have emerged as an alternative green source for practising a circular economy. This research aimed to extract cellulose from bagasse and corn cob waste and utilized in mixed form to prepare bioplastic film. The mixed cellulose was further reinforced with natural substances such as chitosan, bentonite, and P. alba extract. These newly developed bioplastics films were characterized by various physical tests like film thickness, moisture content, water solubility and spectroscopic techniques such as Fourier transform infrared (FTIR), scanning electron microscopy-energy dispersive spectroscopic (SEM-EDX), thermal gravimetric analysis (TGA), and ultraviolet-visible (UV-Vis) spectroscopy for opacity testing. The results revealed the enhanced bioplastic thermal and mechanical characteristics through robust interactions between cellulose and bentonite molecules. Moreover, incorporating chitosan solution as reinforcements in bio-composite films resulted in improved water barrier properties. The results indicated lower absorption in the UV range of 250-400 nm, attributed to the absence of UV-absorbing groups. Finally, their biodegradability was tested in soil, and 85.3 % weight loss of bioplastic films was observed after 50 days of the experiment which is the main task of this research. The antimicrobial properties of bioplastic films have been evaluated, and showed an inhibition zone of 16 mm against E. coli. After 12 days of incubation of sherbet berries, complete spoilage is identified in the control group compared to those covered with the bioplastic film. This outcome is attributed to the antioxidant and antimicrobial activities provided by chitosan and P. alba extract in the bioplastic film. The comprehensive outcomes of this study suggest the potential future adoption of these entirely bio-derived, environmentally sustainable and biodegradable bioplastic films as a viable substitute for the plastic packaging currently present in the market.