Association of single nucleotide polymorphisms in heat stress protein 70 (HSP70) and 90 (HSP90) with the susceptibility of Pakistani sheep breeds to hemoparasitic infections.

The present study was designed to report the genotypic and allelic frequency of single nucleotide polymorphism (SNP) at 222 G > A in HSP70 and at ex6-7390T22G in the HSP90 gene of 204 sheep (Baluchi = 11, Kajli = 29, Latti = 06 and Mundri = 158) enrolled from District Rajanpur in Punjab and to report the susceptibility of these sheep to the blood-borne parasitic infection. The tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) approach revealed a significant variation (p < 0.001) in the genotype frequency of four enrolled sheep breeds at SNP 222 G > A in the HSP70 gene while the allelic frequency remained unaffected (p = 0.08). In all sheep breeds, GG (wild) genotype was most common. T-ARMS-PCR analysis revealed a similar trend for ex6-7390T22G in the HSP90 gene and it was observed that sheep had significantly higher wild-type (GG) (p < 0.05) at the studied SNPs. Studied epidemiological factors (sex and sampling sites) were not found associated with both SNPs. Chi-square test revealed that no specific genotype and allelic frequency at 222 G > A in HSP70 and at ex6-7390T22G in the HSP90 gene of the enrolled sheep breed was associated with the susceptibility to blood-borne parasitic infection (p > 0.05). In conclusion, we are reporting that Pakistan is blessed to have majority of sheep, from all breeds, having wild genotype at analyzed SNPs in heat stress genes. We highly recommend the genotypic screening of sheep before their selection as breeders to reduce the possibility of having sheep with polymorphic genotypes at 222 G > A in HSP70 and at 7390T22G in HSP90 genes that will improve the profitability and sustainability of animal production systems in Pakistan.

Quantitative phytochemical profile, cholinesterase enzyme inhibition assay, antibacterial and antioxidant activities of Sarcococca saligna.

Aqueous methanol extracts of Sarcococca saligna leaves and roots were used in this work to explore its phytochemical contents, antioxidant, enzyme inhibition and antibacterial activities. Total phenolic contents were found to be in higher concentrations then total flavonoids contents in aqueous methanolic extracts of leaves. Antioxidant activity was performed using DPPH radical scavenging assay. In our findings both leaves and roots extracts were found to show substantial antioxidant potential. Aqueous methanolic extracts of both the leaves and roots gave significant inhibition against butyryl cholinesterase whereas against acetyl cholinesterase extracts of roots gave significant inhibition. The results were compared with the standard drug Eserine. The aqueous methanolic extract of leaves, roots and crude saponins isolated from leaf extracts gave moderate to significant antibacterial activity against the tested bacterial strains using agar disc diffusion method. According to the conclusions, S. saligna possesses significant antioxidant, enzyme inhibition, and antibacterial activities. Hence it is assumed that S. saligna has the potential to be used in the discovery and development of new bioactive compounds.

Antileishmanial Agents Co-loaded in Transfersomes with Enhanced Macrophage Uptake and Reduced Toxicity.

The prime objective of this study was to develop amphotericin B (AMB) and rifampicin (RIF) co-loaded transfersomal gel (AMB-RIF co-loaded TFG) for effective treatment of cutaneous leishmaniasis (CL). AMB-RIF co-loaded TF was prepared by the thin-film hydration method and was optimized based on particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (%EE), and deformability index. Similarly, AMB-RIF co-loaded TFG was characterized in terms of rheology, spread ability, and pH. In vitro, ex vivo, and in vivo assays were performed to evaluate AMB-RIF co-loaded TF as a potential treatment option for CL. The optimized formulation had vesicles in nanosize range (167 nm) with suitable PDI (0.106), zeta potential (- 19.05 mV), and excellent %EE of RIF (66%) and AMB (85%). Moreover, it had appropriate deformability index (0.952). Additionally, AMB-RIF co-loaded TFG demonstrated suitable rheological behavior for topical application. AMB-RIF co-loaded TF and AMB-RIF co-loaded TFG showed sustained release of the incorporated drugs as compared to AMB-RIF suspension. Furthermore, RIF permeation from AMB-RIF co-loaded TF and AMB-RIF co-loaded TFG was enhanced fivefold and threefold, whereas AMB permeation was enhanced by eightfold and 6.6-fold, respectively. The significantly different IC50, higher CC50, and FIC50 (p < 0.5) showed synergistic antileishmanial potential of AMB-RIF co-loaded TF. Likewise, reduced lesion size and parasitic burden in AMB-RIF co-loaded TF-treated mouse group further established the antileishmanial effect of the optimized formulation. Besides, AMB-RIF co-loaded TFG showed a better safety profile. This study concluded that TFG may be a suitable carrier for co-delivery of AMB-RIF when administered topically for the treatment of CL.

Moxifloxacin and gemifloxacin mediates its antispasmodic profile via ATP-sensitive potassium channels: An in-vitro bioassay study.

Moxifloxacin and gemifloxacin were tested on isolated rabbits' jejunal preparations as little is known about its effects on gastrointestinal tissues. Moxifloxacin and gemifloxacin were tested in concentrations 0.01-10µg/mL for possible effect(s) on isolated rabbits' jejunal preparations. The drugs were applied on spontaneous, on low K+ (20mM)-induced contractions and on high K+ (80mM)-induced contractions. Response was plotted as % of its respective controls. EC50 for Moxifloxacin and Gemifloxacin on spontaneous (without Glibenclamide) contractions are 2.83±0.5µg/mL and 1.11±0.2µg/mL, respectively. Moxifloxacin and Gemifloxacin relaxed the low K+ (20mM) -induced contractions, which were inhibited in presence of Glibenclamide (3µM). Our result indicates that the relaxant activity of Moxifloxacin and Gemifloxacin is mediated possibly through activation of ATP-sensitive potassium channels (KATP). The relaxant effect of Moxifloxacin and Gemifloxacin is predominantly mediated by activation of ATP-Sensitive potassium channels (KATP), which could be cause of one of relaxing mechanisms.

GC/MS analysis, anti-leishmanial and relaxant activity of essential oil of Chenopodium ambrosioides (L.) from Malakand region.

Chenopodium ambrosioides is abundantly available in Malakand region. As constituents and concentrations of essential oils vary based on its geographical location, we carried our current study to extract and evaluate its possible relaxant activity in rabbits' jejunum and anti-leishmanial activity against promastigotes of Leishmania tropica. The essential oil was obtained from aerial fresh parts through steam distillation followed by GC/MS analysis. Antispasmodic activity was performed on spontaneous and KCl induced contractions. Curves for calcium concentration response (CCRCs) were prepared with and without different concentrations of essential oils and verapamil - a standard calcium channel blocker as per our reported procedures. GC/MS analysis indicated that the essential oil contains 4-carene (56.59%) and o-cymene (41.46%), the two most abundant compounds previously reported from this species. The LD50 value for acute toxicity is 279.66±2.2mg/kg. The essential oil have significant antileishmanial activity with LC50 of Log10 (1.83±0.0026) ×10-6mg/ml, potent relaxant activity on rabbits' jejunal preparations with respective EC50 = 1.46±0.15mg/ml for spontaneous activity. For KCl (80mM) induced contractions, EC50=0.26±0.02mg/ml. In CCRCs, the oil produced a right shift as exhibited by verapamil. More, its relaxant activity, which is mediated through calcium channel blocking mechanism, proves a rationale for its traditional use in gut spasm.

Azithromycin induced contractile responses of intestinal smooth muscles: A mechanistic approach.

The current work is documented to investigate the actions of azithromycin on intestinal smooth muscles as there are reports of gastrointestinal upsets with use of azithromycin. Azithromycin was tested on rabbit's jejunal and rat's ileal preparations in test concentrations (µM) of 0.01, 0.03, 0.1, 0.3, 1, 3, 5, 10 and 15µM. After mounting the tissues in organ bath containing Tyrode's solution, spasmogenic activity of azithromycin was observed. To explore its possible mechanisms, response of azithromycin was noted in the presence of 0.3µM atropine, 3µM loratadine, 0.3µM ondansetron, 10µM metoclopramide, 0.3µM verapamil, 1µM propranolol, 3µM amiodarone and combination of 0.3µM each atropine, ondansetron, verapamil and propranolol (AOVP). Mean % Emax for azithromycin was 67.6±1.6 and 54.0±2.1 (% of ACh max) for rabbit's jejunal and rat's ileal preparations, respectively. The Mean % Emax for azithromycin in the presence of various antagonists for rabbit's jejunal and rat's ileal preparations was as: 2.4±0.1 and 11.4±1.3 with atropine; 67.9±2.0 and 50.7±1.9 with loratadine; 27.5±0.5 and 34.0±2.9 with ondansetron; 88.4±1.2 and 79.1±3.8 with metoclopramide; 13.6±1.2 and 22.3±2.5 with verapamil; 10.2±2.1 and 15.6±1.4 with propranolol; 68.4±1.3 and 58.0±3.4 with amiodarone. Results reveal that the spasmogenic response of azithromycin is mainly mediated through muscarinic receptors. However, we found involvement of mixed pathway including serotonergic receptors, voltage gated calcium channels and voltage gated sodium channels.

Relaxant activity of different fractions of fruits of Rosa moschata J.

The current work is an attempt to know that in which fraction(s) the relaxant constituents of Rosa moschata concentrate. Crude methanolic extract of Rosa moschata was prepared as per our reported procedure. Sub fractions of methanol extract were extracted with different solvents in increasing order of polarity i.e. n-hexane > chloroform > ethyl acetate > n-butanol > residual aqueous fractions. Different concentrations (0.01, 0.03, 0.1, 0.3, 1, 3, 5 and 10 mg/ml) of the fractions were tested on spontaneous contractions and KCl induced contractions on rabbits' jejunal preparations. Calcium Concentration Response Curves (CCRCs) in the presence and absence of the test fractions using verapamil were constructed to understand its mechanisms. EtOA fraction was more relaxant with EC50 values 0.812±0.149 mg/ml on spontaneous and 2.01±0.08 mg/ml on KCl induced contractions. we also found right shift in its EC50 values expressed as log [Ca++]M values. In presence of 0.3 mg/ml EtOA fraction, its EC50 value was -2.22±0.035 vs control EC50 -2.71±0.21. For n-BuOH fraction, EC50 value was -1.82±0.00 vs control with EC50 -2.28±0.049 at concentration of 0.3 mg/ml. Ethyl acetate fraction of Rosa moschata was more potent and is therefore can be a target for activity guided isolation of calcium channel antagonists.

Evaluation of safety profile and stress suppressant activity of Rosa moschata in mice.

Stress is a state that seriously disturbs psychological or physiological homeostasis of the body and subsequently affects the morphology and function of the hippocampus. Currently available anti-stress medications provide limited benefits with cost of severe adverse effects. In the present study, effect of Rosa moschata extract was evaluated using acute restraint model in mice. The stress suppressant activity of Rosa moschata was evaluated by using elevated plus maze test (EPM), dark light box test and open field test (OFT) following restraint stress protocol. Results showed that the Rosa moschata extract significantly enhanced the number of transitions and the time spent in the open arm in the EPM, increased the number of transitions and time spent in the light compartment of the dark light box, and also enhanced the locomotor activity in OFT, as compared to the stress group. In addition, LD50 of the plant extract is greater than 5000mg/Kg. Thus the findings of our studies show that Rosa moschata significantly alleviates stress following the acute restraint stress in mice. Further studies dealing with underlying mechanism and characterization of active fraction/compound may provide an alternative therapy for stress and related neurological conditions.

Antispasmodic and antidiarrhoeal activity of the fruit of Rosa moschata (J).

BACKGROUND: The fruit of Rosa moschata has traditionally been used for the treatment of abdominal spasm and diarrhoea. Therefore, the aim of this study was to investigate mechanism(s) responsible for its medicinal use in gut spasm and diarrhea. METHODS: Hydro-methanolic extract of Rosa moschata (Rm.Cr) was studied in isolated rabbit's jejunal preparations for possible antispasmodic activity. Based upon in vitro relaxant activity in isolated gut preparations, in vivo antidiarrheal activity was carried out in mice to confirm its antidiarrheal effect. Acute toxicity study was performed to determine safe dose range before in vivo experiments. RESULTS: In isolated rabbits' jejunal preparations, Rm.Cr inhibited the spontaneous and high K+-induced contractions with respective EC50 values of 0.66 (0.44-0.97; n = 5) and 2.28 mg/mL (1.43-3.62; n = 5), like that of verapamil. This suggests the presence of calcium channel blocking (CCB) activity as a possible mode of action. The Ca++ channel blocking activity was further confirmed when pre-treatment of isolated jejunums with Rm.Cr (1-5 mg/mL) caused a rightward shift in the Ca++ concentration-response curves (CRCs), similar to verapamil. Rm.Cr was safe up to 2000 mg/kg for in vivo acute toxicity. Rm.Cr provided 55% and 80% protection from diarrhoea in respective doses of 100 mg/kg and 1000 mg/kg. These data indicates that the crude extract of Rosa moschata possesses Ca++ antagonist-like constituent(s), which explains its inhibitory effect on gut motility; a mechanism that underlies its antidiarrheal and antispasmodic activities. CONCLUSION: The study shows that the crude extract of fruits of Rosa moschata possesses antispasmodic effects mediated possibly through voltage gated Ca++ channel blockade, which provides sound pharmacological base to its medicinal use in gut spasms and diarrhoea, though additional mechanism(s) cannot be ruled out.

Joint monitoring of mean and variance using Max-EWMA control chart under lognormal process with application to engine oil data.

The control charts are frequently employed in process monitoring to assess the average and variability of a process, assuming a normal distribution. However, it is worth noting that some process distributions tend to exhibit a positively skewed distribution, such as the lognormal distribution. This article proposed a maximum exponential weighted moving average control chart for joint monitoring of mean and variance under a lognormal process. The proposed control chart is evaluated by using the run length profile such as ARL and SDRL. The Monte Carlo simulation is conducted by using the R language to find the run length profile. An application is presented to demonstrate the design of the proposed control chart.

Enhancing performance in the presence of outliers with redescending M-estimators.

In real-life situations, we have to analyze the data that contains the atypical observations, and the presence of outliers has adverse effects on the performance of ordinary least square estimates. In this situation, redescedning M-estimators, proposed by Huber (1964), are used to tackle the effects of outliers to increase the efficiency of least square estimates. In this study, we introduce a redescending M-estimator designed to generate robust estimates by mitigating the influence of outlier observations, even when the tuning constant is set to low values. This innovative estimator exhibits enhanced linearity at its core and maintains continuity throughout its range. Our proposed estimator stands out for its novelty, simplicity, differentiability, and practical applicability across real-world scenarios. The results of the proposed redescedning M-estimators are compared with existing robust estimators using an extensive simulation study. Two examples based on real-life data are also added to validate the performance of the suggested function. The formulated redescedning M-estimator produced efficient results as compared to all the considered redescedning M-estimators.

A support vector machine based drought index for regional drought analysis.

The increased global warming has increased the likelihood of recurrent drought hazards. Potential links between the frequency of extreme weather events and global warming have been suggested by earlier research. The spatial variability of meteorological factors over short distances can cause distortions in conclusions or limit the scope of drought analysis in a particular region when extreme values predominate. Therefore, it is challenging to make trustworthy judgments regarding the spatiotemporal characteristics of regional drought. This study aims to improve the quality and accuracy of regional drought characterization and the process of continuous monitoring. The new drought indicator presented in this study is called the Support Vector Machine based drought index (SVM-DI). It is created by adding different weights to an SVM-based X-bar chart that is displayed with regional precipitation aggregate data. The SVM-DI application site is located in Pakistan's northern area. Using the Pearson correlation coefficient for pairwise comparison, the study compares the SVM-DI and the Regional Standard Precipitation Index (RSPI). Interestingly, compared to RSPI, SVM-DI shows more pronounced regional characteristics in its correlations with other meteorological stations, with a significantly lower Coefficient of Variation. These results confirm that SVM-DI is a useful tool for regional drought analysis. The SVM-DI methodology offers a unique way to reduce the impact of extreme values and outliers when aggregating regional precipitation data.

New adaptive EWMA CV control chart with application to the sintering process.

This research presents a new adaptive exponentially weighted moving average control chart, known as the coefficient of variation (CV) EWMA statistic to study the relative process variability. The production process CV monitoring is a long-term process observation with an unstable mean. Therefore, a new modified adaptive exponentially weighted moving average (AAEWMA) CV monitoring chart using a novel function hereafter referred to as the "AAEWMA CV" monitoring control chart. the novelty of the suggested AAEWMA CV chart statistic is to identify the infrequent process CV changes. A continuous function is suggested to be used to adapt the plotting statistic smoothing constant value as per the process estimated shift size that arises in the CV parametric values. The Monte Carlo simulation method is used to compute the run-length values, which are used to analyze efficiency. The existing AEWMA CV chart is less effective than the proposed AAEWMA CV chart. An industrial data example is used to examine the strength of the proposed AAEWMA CV chart and to clarify the implementation specifics which is provided in the example section. The results strongly recommend the implementation of the proposed AAEWMA CV control chart.

A redescending M-estimator approach for outlier-resilient modeling.

The OLS model is built on the assumption of normality in the distribution of error terms. However, this assumption can be easily violated, especially when there are outliers in the data. A single outlier can disrupt the normality assumption of error terms, making the OLS model less effective. In such situations, M-estimators (MEs) come into play to obtain reliable estimates. We introduce a redescending M-estimators (RME) for robust regression to handle datasets with outliers. The proposed RME produces more robust estimates by effectively managing the influence of outliers, even at lower values of the tuning constant. We compared the performance of this estimator with existing RMEs using real-life data examples and an extensive simulation study. The results show that our suggested RME is more efficient than the compared ME in various situations.

Adaptive multivariate dispersion control chart with application to bimetal thermostat data.

Adaptive EWMA (AEWMA) control charts have gained remarkable recognition by monitoring productions over a wide range of shifts. The adaptation of computational statistic as per system shift is the main aspect behind the proficiency of these charts. In this paper, a function-based AEWMA multivariate control chart is suggested to monitor the stability of the variance-covariance matrix for normally distributed process control. Our approach involves utilizing an unbiased estimator applying the EWMA statistic to estimate the process shift in real-time and adapt the smoothing or weighting constant using a suggested continuous function. Preferably, the Monte Carlo simulation method is utilized to determine the characteristics of the suggested AEWMA chart in terms of proficient detection of process shifts. The underlying computed results are compared with existing EWMA and existing AEWMA charts and proved to outperform in providing quick detection for different sizes of shifts. To illustrate its real-life application, the authors employed the concept in the bimetal thermostat industry dataset. The proposed research contributes to statistical process control and provides a practical tool for the solution while monitoring covariance matrix changes.

A Weibull process monitoring with AEWMA control chart: an application to breaking strength of the fibrous composite.

In recent times, there has been a growing focus among researchers on memory-based control charts. The Exponentially Weighted Moving Average (EWMA) and Cumulative Sum (CUSUM) charts and the adaptive control charting approaches got the attention. Control charts are commonly employed to oversee processes, assuming the monitored variable follows a normal distribution. However, it's worth noting that this assumption does not hold true in many real-world situations. The use of the algebraic expression for normalization, which can be used for all kinds of skewed distributions with a closed-form distribution function, using the proposed continuous function to adapt a smoothing constant, motivates this study. In the present manuscript, we design an EWMA statistic-based adaptive control chart to monitor the irregular variations in the mean of two parametric Weibull distribution and use Hasting approximation for normalization. The adaptive control charts are used to update the smoothing constant according to the estimated shift. Here we use the proposed continuous function to adapt the smoothing constant. The average run length and standard deviation of run length are calculated under different parameter settings. The effectiveness of the proposed chart is argued in terms of ARLs over the considered EWMA chart through Monte-Carlo (MC) simulation method. The proposed chart is examined, followed by a real data set to demonstrate the design and application procedures.

Adsorption Behavior of Methylene Blue Cationic Dye in Aqueous Solution Using Polypyrrole-Polyethylenimine Nano-Adsorbent.

In this work, a polypyrrole-polyethyleneimine (PPy-PEI) nano-adsorbent was successfully synthesized for the removal of methylene blue (MB) from an aqueous solution. Synthetic dyes are among the most prevalent environmental contaminants. A new conducting polymer-based adsorbent called (PPy-PEI) was successfully produced using ammonium persulfate as an oxidant. The PEI hyper-branched polymer with terminal amino groups was added to the PPy adsorbent to provide more effective chelating sites for dyes. An efficient dye removal from an aqueous solution was demonstrated using a batch equilibrium technique that included a polyethyleneimine nano-adsorbent (PPy-PEI). The best adsorption parameters were measured at a 0.35 g dosage of adsorbent at a pH of 6.2 and a contact period of 40 min at room temperature. The produced PPy-PEI nano-adsorbent has an average particle size of 25-60 nm and a BET surface area of 17 m2/g. The results revealed that PPy-PEI nano-composite was synthesized, and adsorption was accomplished in the minimum amount of time. The maximum monolayer power, qmax, for MB was calculated using the isothermal adsorption data, which matched the Langmuir isotherm model, and the kinetic adsorption data, which more closely fitted the Langmuir pseudo-second-order kinetic model. The Langmuir model was used to calculate the maximum monolayer capacity, or qmax, for MB, which was found to be 183.3 mg g-1. The as-prepared PPy-PEI nano-adsorbent totally removes the cationic dyes from the aqueous solution.

Vitamin B6 and homocysteine levels in carbamazepine treated epilepsy of Khyber Pakhtunkhwa.

OBJECTIVES: The study focused on the plasma levels of vitamin B6 and homocysteine in different genotypes of MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes in carbamazepine resistant epilepsy in the population of Khyber Pakhtunkhwa. METHODOLOGY: Patients who were possible candidates for carbamazepine therapy were followed for six months for their seizure control. Plasma levels of vitamin B6 and homocysteine were determined using immunoassay based techniques at baseline and after six months. MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes were genotyped using restriction fragment length polymorphisms. Seizure control during therapy was recorded on a standardized proforma. RESULTS: Low vitamin B6 levels and hyperhomocysteinemia were found in 61.7% of resistant patients (n=34). Resistant patients had the following frequencies of variant genotypes (677CT=38.1% and 677TT=24.4%; 1298AC=42.2% and 1298CC=26.1%; 588CT= 47.6% and 315TT= 33.3%) of MTHFR (C677T and A1298C) and GABRG2 (C588T and C315T) genes. A significant decline in vitamin B6 (P<0.0001) and hyperhomocysteinemia were found in variant genotypes of MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes. CONCLUSION: Following six months of carbamazepine of therapy in heterozygous variant genotypes of MTHFR (677CT and 1298AC) and GABRG2 (588CT and 315CT) genes, we observed a significant fall in vitamin B6 levels and hyperhomocysteinemia.

The Development of Non-Enzymatic Glucose Biosensors Based on Electrochemically Prepared Polypyrrole-Chitosan-Titanium Dioxide Nanocomposite Films.

The performance of a modified electrode of nanocomposite films consisting of polypyrrole-chitosan-titanium dioxide (Ppy-CS-TiO2) has been explored for the developing a non-enzymatic glucose biosensors. The synergy effect of TiO2 nanoparticles (NPs) and conducting polymer on the current responses of the electrode resulted in greater sensitivity. The incorporation of TiO2 NPs in the nanocomposite films was confirmed by X-ray photoelectron spectroscopy (XPS) spectra. FE-SEM and HR-TEM provided more evidence for the presence of TiO2 in the Ppy-CS structure. Glucose biosensing properties were determined by amperommetry and cyclic voltammetry (CV). The interfacial properties of nanocomposite electrodes were studied by electrochemical impedance spectroscopy (EIS). The developed biosensors showed good sensitivity over a linear range of 1-14 mM with a detection limit of 614 µM for glucose. The modified electrode with Ppy-CS nanocomposite also exhibited good selectivity and long-term stability with no interference effect. The Ppy-CS-TiO2 nanocomposites films presented high electron transfer kinetics. This work shows the role of nanomaterials in electrochemical biosensors and describes the process of their homogeneous distribution in composite films by a one-step electrochemical process, where all components are taken in a single solution in the electrochemical cell.

Current statins show calcium channel blocking activity through voltage gated channels.

BACKGROUND: Statins are used for treatment of hypercholestremia. Common adverse reports associated with use of statins are generalized bodyache, rhabdomyolysis, muscles weakness and gastrointestinal disorders. The current work is an attempt to explain how smooth muscles of gastrointestinal tissues are affected by the current statins (Simvastatin, atorvastatin, fluvastatin and rosuvastatin). METHODS: Effects of the current statins were studied on spontaneous activity of isolated rabbits' jejunal preparations. Different molar concentrations (10(-12)-10(-2)M) of the statins were applied on spontaneously contracting rabbits' jejunal preparations. As statins relaxed spontaneous activity, so we tested the statins on KCl (80 mM) induced contractions in similar test concentrations. Positive relaxant statins were tested again through construction of Calcium Concentration Response Curves (CCRCs) in the absence and presence of the statins using verapamil, a standard calcium channel blocker. CCRCs of statins were compared with CCRCs of verapamil. RESULTS: Simvastatin, atorvastatin, fluvastatin and rosuvastatin relaxed the spontaneous and KCl-induced contractions. IC50 for simvastatin on spontaneous rabbit's jejunal preparations is -5.08 ± 0.1 Log 10 M. Similarly, IC50 for KCl-induced contractions is -4.25 ± 0.01 Log 10 M. Mean IC50 (Log 10 M) for atorvastatin on spontaneous rabbit's jejunal preparations and KCl-induced contractions are -5.19 ± 0.07 and -4.37 ± 0.09, respectively. Fluvastatin relaxed spontaneous activity of rabbits' jejunal preparations with an IC50 (Log 10 M) -4.5 ± 0.03. Rosuvastatin relaxed spontaneous as well as KCl (80 mM) induced contractions with respective IC50 (Log 10 M) -3.62 ± 0.04 and -4.57 ± 0.06. In case of CCRCs, tissues pre-treated with 4.6 µg/ml of simvastatin, have IC50 = -1.84 ± 0.03 [log (Ca(++)) M] vs control IC50 = -2.54 ± 0.04 [log (Ca(++)) M]. Similarly, atorvastatin, fluvastatin and rosuvastatin produced significant right shift in IC50 for CCRCs (P ≤ 0.05). In case of verapamil, IC50 for control curves is -2.45 ± 0.06 [log (Ca (++)) M], while IC50 in presence of verapamil (0.1 µM) is -1.69 ± 0.05 [log (Ca (++)) M]. Statins produced right shift in the IC50 of CCRCs. The effects of statins are like that of effects of verapamil, a standard calcium channel blocker. CONCLUSIONS: Our findings suggest that current statins have calcium antagonistic effects that act on voltage gated calcium channels that may provide a rationale for cause muscle weakness and gastrointestinal disorders.