Effects of Ziziphus Honey on Bone Healing of the Extracted Tooth Socket by Evaluating Osteopontin Levels.

OBJECTIVE: To evaluate the effect of Ziziphus honey on the healing of post-extraction alveolar sockets by estimating the levels of osteopontin (OPN) in humans. STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Dental section of the Lahore General Hospital, Lahore, Pakistan, from March 2020 to February 2021. METHODOLOGY: A total of 30 patients were included in the study. The mean age was 35 ± 0.28 years. The participants were adults undergoing permanent molar extraction, randomly divided into two groups, a control group and an experimental group. After tooth extractions in both groups, 1ml of Ziziphus honey was administered into the extracted tooth socket of the experimental group while no intervention was done to the control group. Saliva samples were collected on day 0 before tooth extraction and on days 3 and 7 after tooth extractions. Enzyme-linked immunosorbent assay (ELISA) technique was used to measure the levels of OPN in the saliva sample. Radiographic evaluation was also done with the help of periapical radiographs using Image J® software. To find out the significance of the outcome in experimental and control groups, an unpaired t-test was applied. A p-value <0.05 was considered statistically significant. RESULTS: A total of 30 participants were selected for the study, of which 16 were females and 14 were males. The OPN levels between the control vs. experimental groups were (22.55 ± 2.45 vs. 23.31 ± 2.38; p = 0.4) on day 0, (30.95 ± 2.96 vs. 53.29 ± 4.69; p = 0.001) on day 3, and (55.33 ± 4.52 vs. 81.90 ± 4.49; p = 0.001) on day 7. CONCLUSION: Increased salivary levels of the OPN in the experimental group with the use of Ziziphus honey suggests better bone healing as compared to the control group. KEY WORDS: Extraction tooth, Honey, Osteopontin, Ziziphus, Bone healing.

Amyloid-ß and caspase-1 are indicators of sepsis and organ injury.

Background: Sepsis is a life-threatening condition that results from a dysregulated host response to infection, leading to organ dysfunction. Despite the prevalence and associated socioeconomic costs, treatment of sepsis remains limited to antibiotics and supportive care, and a majority of intensive care unit (ICU) survivors develop long-term cognitive complications post-discharge. The present study identifies a novel regulatory relationship between amyloid-ß (Aß) and the inflammasome-caspase-1 axis as key innate immune mediators that define sepsis outcomes. Methods: Medical ICU patients and healthy individuals were consented for blood and clinical data collection. Plasma cytokine, caspase-1 and Aß levels were measured. Data were compared against indices of multiorgan injury and other clinical parameters. Additionally, recombinant proteins were tested in vitro to examine the effect of caspase-1 on a functional hallmark of Aß, namely aggregation. Results: Plasma caspase-1 levels displayed the best predictive value in discriminating ICU patients with sepsis from non-infected ICU patients (area under the receiver operating characteristic curve=0.7080). Plasma caspase-1 and the Aß isoform Aßx-40 showed a significant positive correlation and Aßx-40 associated with organ injury. Additionally, Aß plasma levels continued to rise from time of ICU admission to 7 days post-admission. In silico, Aß harbours a predicted caspase-1 cleavage site, and in vitro studies demonstrated that caspase-1 cleaved Aß to inhibit its auto-aggregation, suggesting a novel regulatory relationship. Conclusions: Aßx-40 and caspase-1 are potentially useful early indicators of sepsis and its attendant organ injury. Additionally, Aßx-40 has emerged as a potential culprit in the ensuing development of post-ICU syndrome.

The Bronchodilator Potential of Astragalus sarcocolla: An in vitro Experiment.

OBJECTIVE: To evaluate the bronchodilatory mechanism of Astragalus sarcocolla (ASE) extract on tracheal smooth muscles of rabbits. STUDY DESIGN: In-vitro experimental study. Place and Duration of the Study: The animal house of CMH Lahore Medical College, Lahore, and Institute of Dentistry, NUMS, from October 2022 to May 2023. METHODOLOGY: Six rabbits were randomly divided into four groups. After euthanising the rabbit, the trachea was carefully dissected out and stabilised in Kreb's Henseleit solution for 30 minutes and then, stimulated by acetylcholine (Ach) 1µm, under mimicked physiological conditions. Group I served as the control group with tracheal smooth muscles stabilised with 1g tension. In Group II (positive control), tracheal smooth muscles were stimulated by potassium chloride (KCl) (80 mM and 25 mM, respectively) to get maximum tracheal smooth muscle contractions. Later, the tissue was exposed to theophylline with three molar concentrations 0.2, 0.4, 0.6, and 0.8 mM, and cumulative dose response curves were formed. In Group III (ASE group), tracheal smooth muscles were stimulated by KCl (80 mM and 25 mM) and was exposed to increasing concentration of ASE. In group IV, tissue was stimulated by KCl (25 mM) and glibenclamide (3 µM), later exposed to increasing concentration of ASE to confirm the bronchodilatory mechanism. The change in isometric contraction of the tissue was recorded using the force displacement transducer connected to a PowerLab data acquisition system. Concentration response curves were drawn, and median effective concentrations (EC50 values) and percentage inhibition were calculated. Non-linear regression was applied for the analysis of the concentration-response curves. RESULTS: ASE inhibited the KCl-induced low potassium (25 mM) contractions (EC50 = 0.38 mg/ml, 95% CI: 0.04 - 0.38, n = 6). It only partially inhibited the high potassium-induced contractions in tracheal smooth muscles. Pretreatment with glibenclamide showed a rightward shift of the dose-response curve. Theophylline and ASE significantly reduced the low K+ induced smooth muscle contractions in comparison to the control group (p <0.001, each). CONCLUSION: Astragalus sarcocolla extract produced bronchodilator effects through the activation of ATP sensitive potassium channels in isolated rabbit trachea. KEY WORDS: Astragalus sarcocolla, Bronchodilators, ATP-sensitive potassium channels, Effective concentration 50, Concentration response curves.

Rasagiline Pharmacokinetics in CYP1A2 Variant Healthy Smokers & Non-smokers in Different Doses.

Objectives: Rasagiline, a drug for Parkinson's disease is metabolized by CYP1A2 enzyme. The objective of the study was to investigate the influence of cytochrome P450 1A2 variants and smoking status of healthy individuals on the pharmacokinetics of rasagiline. Methods: A comparative, open label, interventional, single oral dose, pharmacokinetic study was performed on 108 healthy volunteers in UHS & UVAS, Lahore. Data collection was initiated in June 2016 and ended in January 2018. It was divided in three phases with 1, 2 and 5mg of rasagiline given to a group of 36 volunteers in each phase. Volunteers were sub-divided into six groups of AA smokers, AA non-smokers, AC smokers, AC non-smokers, CC smokers & CC non-smokers on the basis of genotyping and smoking status. Serial blood sampling was performed at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 & 12 hours after administration of rasagiline tablets. Plasma concentrations were determined using High Performance Liquid Chromatography (HPLC) method. Pharmacokinetic (PK) parameters were calculated using software (APO) pharmacological analysis. Results: Analysis of variance (ANOVA) showed significant difference between AA and CC groups. Multiple group comparison with post hoc Tukey's revealed that AA-smokers had significantly less tmax (p<0.001), t1/2 (p<0.012), AUC (p<0.008) and highest Cl (p<0.001) as compared to CC-smokers. The trend was same across all three doses. Conclusion: The study concludes that the systemic metabolism of rasagiline is significantly increased in CYP1A2*AA variants while smoking status did not show consistent difference in PK parameters.

Carbonic Anhydrase IX and Hypoxia Promote Rat Pulmonary Endothelial Cell Survival during Infection.

Low tidal volume ventilation protects the lung in mechanically ventilated patients. The impact of the accompanying permissive hypoxemia and hypercapnia on endothelial cell recovery from injury is poorly understood. CA (carbonic anhydrase) IX is expressed in pulmonary microvascular endothelial cells (PMVECs), where it contributes to CO2 and pH homeostasis, bioenergetics, and angiogenesis. We hypothesized that CA IX is important for PMVEC survival and that CA IX expression and release from PMVECs are increased during infection. Although the plasma concentration of CA IX was unchanged in human and rat pneumonia, there was a trend toward increasing CA IX in the bronchoalveolar fluid of mechanically ventilated critically ill patients with pneumonia and a significant increase in CA IX in the lung tissue lysates of pneumonia rats. To investigate the functional implications of the lung CA IX increase, we generated PMVEC cell lines harboring domain-specific CA IX mutations. By using these cells, we found that infection promotes intracellular (IC) expression, release, and MMP (metalloproteinase)-mediated extracellular cleavage of CA IX in PMVECs. IC domain deletion uniquely impaired CA IX membrane localization. Loss of the CA IX IC domain promoted cell death after infection, suggesting that the IC domain has an important role in PMVEC survival. We also found that hypoxia improves survival, whereas hypercapnia reverses the protective effect of hypoxia, during infection. Thus, we report 1) that CA IX increases in the lungs of pneumonia rats and 2) that the CA IX IC domain and hypoxia promote PMVEC survival during infection.

The Spasmolytic Effect of Astragalus Sarcocolla on the Intestinal Smooth Muscles of Rabbit In Vitro: Potassium Channel Opening.

Introduction Astragalus species have been widely used in Chinese herbal medicine to treat gastrointestinal and inflammatory disorders. This study was conducted to evaluate the efficacy of Astragalus sarcocolla (ASE) and to rationalize its medicinal use as an antispasmodic drug for the treatment of spasmodic gastrointestinal and inflammatory disorders associated with increased intestinal motility. Methods The ethanolic extract of ASE was studied to examine its antispasmodic effect on the isolated rabbit ileum preparations, and the contractions were recorded on PowerLab (ADInstruments, Sydney, Australia). Results ASE was able to inhibit spontaneous ileum contractions. It also completely inhibited K+ (25 mM)-induced contractions but was unable to inhibit high K+ (80 mM)-induced sustained contractions. Pretreatment of the tissue with glibenclamide, a potassium channel blocker, caused a rightward shift of the dose-response curve when stimulated with K+ (25 mM) in the presence of an increasing concentration of the extract. Verapamil at very low doses inhibited both the 25 mM and 80 mM K+-induced contractions. Conclusion The results of our study demonstrated the spasmolytic activity of ASE with the potential mechanism of activation of K+ATP, which provides a strong basis for its medicinal use in motility and inflammatory disorders of the intestine.

Prevalence of Self-medication for Acid Peptic Disease amongst People of Manawa, Lahore.

Introduction Acid peptic disease is a common disorder, affecting millions of people worldwide. Its pharmacological management includes proton pump inhibitors, H2 blockers, antacids and mucosal protective agents. Multiple studies in Pakistan have shown increased tendency of population for self-medication. This has serious implications regarding false diagnoses, misuse of drugs and occurrence of adverse effects. The objective of this study was to estimate the prevalence of self-medication among the people of Manawa, Lahore. Methods A cross-sectional study was conducted between January 2019 and June 2019 amongst the general population of Manawa, Lahore. Patients with the typical presentation of acid peptic disease were included in the study. A total of 500 people, fulfilling the inclusion criteria, were chosen. A questionnaire form was adapted from similar studies performed on self-medication. It was divided into two parts. First part included the social and demographic data while the second part consisted of details about the prevalence and factors related to the practice of self-medication amongst acid peptic disease (APD) patients. The data collected was transcribed into SPSS 22.0 (IBM Corp., Armonk, NY) for statistical analysis. All the categorical variables were analyzed as frequencies and percentages. No statistical comparisons were done as it was a descriptive, exploratory study. Results Out of 500 participants, 404 were females and 96 were males. Most of them were middle-aged (53%) and illiterate (68.4%). Number of participants who practiced self-medication was found to be 313 (62.6%). The highest prevalence of self-medication was found for proton pump inhibitors (43.1%), followed by antacids (23.6%), unknown homeopathic and Hakeem medicine (20.4%) and H2 blockers (12.8%). The most common reasons stated for self-medication included inability to afford medical consultation (44.2%), lack of knowledge about drug side effects (35.8%), easy access to Hakeem and homeopathic medicines (27.6% and 4.8%, respectively) and inaccessibility to doctors (19.2%). Conclusion A large majority of people in Manawa practise self-medication for acid peptic disease, owing to multiple reasons.

Evaluation of anti-urolithiatic and diuretic activities of watermelon (Citrullus lanatus) using in vivo and in vitro experiments.

Traditionally, Citrullus lanatus is known to have protective properties in kidney diseases and for having the ability to clear urine. Current study aims to validate the traditional uses of C. lanatus by evaluation of anti-urolithiatic and diuretic activities using in vivo and in vitro experiments. Male Wistar rats were used for in vivo anti-urolithiatic and diuretic activities. Supersaturated solution of calcium and oxalate was used for in vitro crystallization study. Hematoxylin & eosin staining was used for histopathological evaluation of kidney. In the in vivo rat model of urolithiasis, the pulp extract reduced calcium oxalate (CaOX) crystal count in both kidney and urine. The pulp extract also increased the urinary pH and output, and prevented the weight loss. Serum analysis showed elevation in creatinine clearance and reduction in urea and creatinine levels. Urinary analysis demonstrated that pulp extract restored altered phosphate, calcium, oxalate, and citrate levels. In the in vivo rat model of diuresis; the pulp extract produced diuresis, reduced serum chloride levels, and elevated urinary sodium and chloride levels. In the in vitro crystallization experiment, pulp extract inhibited the aggregation phase. Seed extract failed to show any convincing results. GC-MS analysis revealed the presence of steroids and alkanes as the major constituents of pulp extract, which might be responsible for anti-urolithiatic activity; however, further studies are required for isolation and identification of active constituents. Current study validated the traditional uses of watermelon and demonstrated that pulp extract possessed significant anti-urolithiatic and diuretic activities.