Background and Objectives: We have recently reported that stains have calcium channel blocking activity in isolated jejunal preparations. In this study, we examined the effects of atorvastatin and fluvastatin on blood vessels for a possible vasorelaxant effect. We also studied the possible additional vasorelaxant effect of atorvastatin and fluvastatin, in the presence of amlodipine, to quantify its effects on the systolic blood pressure of experimental animals. Materials and Methods: Atorvastatin and fluvastatin were tested in isolated rabbits’ aortic strip preparations using 80mM Potassium Chloride (KCl) induced contractions and 1 micro molar Norepinephrine (NE) induced contractions. A positive relaxing effect on 80 mM KCl induced contractions were further confirmed in the absence and presence of atorvastatin and fluvastatin by constructing calcium concentration response curves (CCRCs) while using verapamil as a standard calcium channel blocker. In another series of experiments, hypertension was induced in Wistar rats and different test concentrations of atorvastatin and fluvastatin were administered in their respective EC₅₀ values to the test animals. A fall in their systolic blood pressure was noted using amlodipine as a standard vasorelaxant drug. Results: The results show that fluvastatin is more potent than amlodipine as it relaxed NE induced contractions where the amplitude reached 10% of its control in denuded aortae. Atorvastatin relaxed KCL induced contractions with an amplitude reaching 34.4% of control response as compared to the amlodipine response, i.e., 39.1%. A right shift in the EC₅₀ (Log Ca++ M) of Calcium Concentration Response Curves (CCRCs) implies that statins have calcium channel blocking activity. A right shift in the EC₅₀ of fluvastatin with relatively less EC₅₀ value (−2.8 Log Ca++ M) in the presence of test concentration (1.2 × 10⁻⁷ M) of fluvastatin implies that fluvastatin is more potent than atorvastatin. The shift in EC₅₀ resembles the shift of Verapamil, a standard calcium channel blocker (−1.41 Log Ca++ M). Conclusions: Atorvastatin and fluvastatin relax the aortic strip preparations predominantly through the inhibition of voltage gated calcium channels in high molar KCL induced contractions. These statins also inhibit the effects of NE induced contractions. The study also confirms that atorvastatin and fluvastatin potentiate blood pressure lowering effects in hypertensive rats.

Background and Objectives: We have recently reported that Fluvastatin, Atorvastatin, Simvastatin and Rosuvastatin have calcium channel antagonistic activities using rabbits’ intestinal preparations. The current study is focused on the effects of Pitavastatin and Lovastatin for possible inhibition of vascular L-Type calcium channels, which may have vasorelaxant effect(s). Combined effects of Pitavastatin and Lovastatin in the presence of Amlodipine were also tested for vasorelaxation. Materials and Methods: Possible relaxing effects of Pitavastatin and Lovastatin on 80 mM Potassium chloride (KCL)-induced contractions and on 1 µM norepinephrine (N.E)-induced contractions were studied in isolated rabbit’s aortic strips preparations. Relaxing effects on 80 mM KCL-induced vascular contractions were further verified by constructing Calcium Concentration Response Curves (CCRCs), in the absence and presence of three different concentrations of Pitavastatin and Lovastatin using CCRCs as negative control. Verapamil was used as a standard drug that has L-Type calcium channel binding activity. In other series of experiments, we studied drug interaction(s) among Pitavastatin, Lovastatin, and amlodipine. Results: The results of this study imply that Lovastatin is more potent than Pitavastatin for having comparatively lower EC₅₀ (7.44 × 10⁻⁵ ± 0.16 M) in intact and (4.55 × 10⁻⁵ ± 0.10 M) in denuded aortae for KCL-induced contractions. Lovastatin amplitudes in intact and denuded aortae for KCL-induced contractions were, respectively, 24% and 35.5%; whereas amplitudes for Pitavastatin in intact and denuded aortae for KCL-induced contractions were 34% and 40%, respectively. A left shift in the EC₅₀ values for the statins was seen when we added amlodipine in EC₅₀ (Log Ca⁺⁺ M). Right shift for CCRCs state that Pitavastatin and Lovastatin have calcium channel antagonistic effects. Lovastatin in test concentration (6.74 × 10⁻⁷ M) produced a right shift in relatively lower EC₅₀ (−2.5 ± 0.10) Log Ca⁺⁺ M as compared to Pitavastatin, which further confirms that lovastatin is relatively more potent. The right shift in EC₅₀ resembles the right shift of Verapamil. Additive effect of Pitavastatin and Lovastatin was noted in presence of amlodipine (p < 0.05). Conclusions: KCL (80 mM)-induced vascular contractions were relaxed by Pitavastatin and Lovastatin via inhibitory effects on L-Type voltage-gated calcium channels. Lovastatin and Pitavastatin also relaxed Norepinephrine (1 µM)-induced contractions giving an insight for involvement of dual mode of action of Pitavastatin and Lovastatin.

OBJECTIVE: To identify the effectiveness and safety of thalidomide in transfusion-dependent beta Thalassemia Major (TDBTM) patients. METHODS: A comprehensive search of PubMed, Cochrane Library, and Embase was conducted between January 01, 2014, and April 17, 2024, using terms like “thalidomide”, “thalidomide”, “α- phthalimidoglutarimide”, “thalassemia”, “beta thalassemia”, “transfusion dependent thalassemia” using Boolean or wildcard operators. Studies published in English with an observational or experimental design, including more than 10 TDBTM patients treated with thalidomide for at least 3 months, were included. The review focused on patients of all ages and genders, evaluating the impact of thalidomide on transfusion requirements. The included trials, involved 780 participants (age range=1.5-27.2 years), showing improvements in hemoglobin, fetal hemoglobin (HbF), serum ferritin, spleen size, and quality of life. National Institute of Health tool was used for quality assessment. RESULTS: After screening 19462 records, 18147 remained after duplicates were removed. Of these, 18138 were excluded, leaving 09 studies for inclusion in the review. Conducted in Pakistan, China, India and Iraq (2014-2024), the studies included a single-arm trial, a double-blinded RCT, and an open-label RCT and Pre-post enrolling 780 participants. Thalidomide (50-150 mg/day) improved hemoglobin, HbF, serum ferritin, spleen size, and quality of life, with a mean follow-up of 13 months. Thalidomide therapy resulted in transfusion independence in 69.6 % (n= 543) patients. Adverse effects were reported in 41.2 % (n=322) patients. Study quality was rated as good. CONCLUSION: Thalidomide is a well-tolerated, safe, and effective treatment for TDBTM patients, but these findings require confirmation through well-designed clinical trials.

Schiff bases synthesized in our laboratory have demonstrated pain-relieving effects through both peripheral and central nervous system pathways. Considering that centrally acting analgesics often affect the muscle tone of the gastrointestinal tract (GIT) and related deep internal organs, this study was conducted to examine potential relaxant effects on blood vessels and GIT smooth muscles. The possible relaxant effects of Schiff bases (SB1 and SB2) on isolated rabbit aortic strips were evaluated. The experiments involved assessing their impact on contractions induced by 80 mM potassium chloride (KCL) and 1 µM norepinephrine (NE). Norepinephrine concentration response curves (N. ECRCs) were constructed in the absence and presence of three different concentrations of SB1 and SB2, using N. ECRCs as a negative control. Terazosin served as a standard α1 receptor blocker. Docking studies were employed to validate the mechanism of action for SB1 and SB2. The study outcomes suggest that SB1 is more potent than SB2, demonstrating lower EC₅₀ values for NE-induced contractions in intact (5.50 × 10⁻⁵ ± 2.23 M) and denuded (5.81 × 10⁻⁵ ± 3.80 M) aortae. For NE-induced contractions, SB1 showed percent relaxation values of 48% and 41% in intact and denuded aortae, respectively. In comparison, SB2 exhibited values of 82.5% and 74%, showing that SB1 is more efficacious than SB2. The rightward shift of N. ECRCs for both SB1 and SB2 confirms their inhibition of α1 receptors. Additive effects of SB1 and SB2 were seen in the presence of verapamil (p < 0.0001). Docking analysis revealed that the compounds can properly bind to the target receptor Gq 1D (P25100). Findings show that both Schiff base SB1 and SB2 produce significant (p < 0.05) vasorelaxation via the α1 receptor blocking mechanism.

Background: To assess the relative effectiveness of diclofenac sodium and gabapentin as preventive analgesics for post-operative pain management in patients having laparotomy. Study Design: Present study was a comparative controlled trial conducted at random. Methodology: Current comparative controlled trial was conducted at random fashion in different surgical and pharmacology departments of Pakistan from December 2022 to June 2023. There were a total of 100 individuals having laparotomy therefore 600 mg capsule of Gabapentin and 100 mg sustain released combination therapy was given to the every patient one hour before to going into the procedure room under doctors direct supervision. All patients were put to sleep using the conventional general anesthetic approach. The patient was moved to the recovery area next to the operating theater once the procedure and extraction were finished and their pain was measured 1to 31 minutes. Finally, all patients were shifted to the ward where the intensity of their pain were measured 60, 121, 241 and 361 minutes respectively. The intermediate time of admission and operation were noted regularly. The bio-statistic version SPSS 2020 were applied for the description of raw data. Results: The mean standard deviation levels of age, gender, BMI, surgery duration and average anesthesia time in both Group-X and Group-Y individuals with gabapentin and diclofenac sodium were (57.18±18.04, 58.21±1.03), (67.11±01.02, 67.11±01.01), (33.10±01.04, 33.10±01.04), (28.10 ± 1.01), (27.11 ±1.01), (118.01±01.01), (128.01±02.02) showed a significant (P≤ 0.05) change. The pain ratings for gabapentin was (9.01±04.01) and diclofenac sodium was (15.25±02.03) for the 361-minute interval. 12-hour period or 721 minutes Compared to Diclofenac sodium, which exhibits a pain intensity of (14.61±04.05), gabapentin showed a considerable decline in pain. Conclusion: The study's findings showed that administering a single oral dosage of gabapentin as a preventive analgesic to patients having major abdominal operations is beneficial for managing post-operative pain since the medication's effects linger longer and decrease the need for rescue analgesics. Keywords: Gabapentin, Laparotomy, Anticonvulsants, glycopyrrolate, analgesics, surgery, abdominal, gynecological.