This review article is built on the beneficial effects of Lactobacillus against different diseases, and a special focus has been made on its effects against neurological disorders, such as depression, multiple sclerosis, Alzheimer’s, and Parkinson’s disease. Probiotics are live microbes, which are found in fermented foods, beverages, and cultured milk and, when administered in an adequate dose, confer health benefits to the host. They are known as “health-friendly bacteria”, normally residing in the human gut and involved in maintaining homeostatic conditions. Imbalance in gut microbiota results in the pathophysiology of several diseases entailing the GIT tract, skin, immune system, inflammation, and gut–brain axis. Recently, the use of probiotics has gained tremendous interest, because of their profound effects on the management of these disease conditions. Recent findings suggest that probiotics enrichment in different human and mouse disease models showed promising beneficial effects and results in the amelioration of disease symptoms. Thus, this review focuses on the current probiotics-based products, different disease models, variable markers measured during trials, and evidence obtained from past studies on the use of probiotics in the prevention and treatment of different diseases, covering the skin to the central nervous system diseases.

Previous studies have shown that Khyber Pakhtunkhwa, Pakistan has a high incidence of epilepsy and a high proportion of low socioeconomic background and high treatment gap. Considering the changes over the past 20 years little is known about the current epidemiological characteristics of epilepsy in Khyber Pakhtunkhwa, Pakistan. The current study was focused to find the impact of various contributing factors on the clinical response to anti-epileptic drugs in the KP population, Pakistan. A total of 315 participants aged 19.1 ± 8.6 years were examined. Mean age of the patients was 18 ± 8.1 year. Epilepsy was high in male patients (64.39%) and urban areas (60.1%). Mostly, 88.6% of patients were belonging to low socioeconomic status background. 42.4% patients have positive family history for epilepsy and 42.8% patients had consanguineous marriages. Middle SES class patients (OR, 2.22 [CI, 0.54–9.1]) were slightly associated with controlled response to CBZ and VPA therapy. Absence seizure (OR, 1.16 [CI, 0.59–2.3]), and Complex partial seizure (OR, 1.29 [CI, 0.58–6.3]) showed good response to CBZ therapy while, Myoclonic seizure (OR, 2.23 [CI, 0.05–8.8]) was responsive to VPA therapy. However, non-compliance (R² 0.82, P < 0.0001) and nature of seizures (R² 0.83, P < 0.0001) were associated with the high risk for poor response to both CBZ and VPA therapy. Epilepsy was high in male patients and in urban areas. Most patients were belonging to low socioeconomic status. Non-compliance, low socioeconomic and nature of seizures strongly predict poor clinical response of anti-epileptic drugs therapy.

Purpose: SCN1A (3184 A>G) and SCN2A (56G>A) gene encodes a subunit of the neuronal voltage-gated sodium channel, which is a target for carbamazepine (CBZ). Recent studies have demonstrated that polymorphism of SCN1A (3184 A>G) and SCN2A (56G>A) was associated with use of CBZ. However, it has not been determined whether the polymorphism affects CBZ or other antiepileptic drug responsiveness. The aim of the study was to establish whether the SCN1A (3184 A>G) and SCN2A (56G>A) polymorphisms of the SCN1A and SCN2A genes affect responsiveness to CBZ. Methods: SCN1A (3184 A>G) and SCN2A (56G>A) gene polymorphisms were genotyped in 93 Khyber Pakhtunkhwa epileptic patients treated with CBZ. The association between CBZ responsiveness and the polymorphism was estimated by adjusting for clinical factors affecting the outcome of therapy. The number of seizure episodes was documented at baseline, and the therapy of each of the 93 patients was followed up. The plasma level of CBZ was determined using reverse-phase high-performance liquid chromatography. SCN1A and SCN2A genes were genotyped using RFLP. Data were analyzed using Graph Pad Prism 6. Results: Mean age of the patients was 18.6±9.3 at the 3rd month and 18.7±9.5 at the 6th month. The baseline dose of CBZ was 468±19.8 mg/d and titrated at the rate of 48±1.4 and 4.0±0.2 mg/d. The difference in plasma level of CBZ was significant (P=0.004) between 3rd and 6th month among different genotypes of SCN1A gene in nonresponder and responder patients. At the 3rd month of the therapy, the poor responders were more likely (P=0.003 and P=0.01) to have variants (3184AG and 3184GG) of SCN1A gene. Similarly, poor responsders were more likely (P=0.0007 and P=0.001) to have variant genotypes (56GA, 56AA) of SCN2A gene at the 3rd month of the therapy. Conclusion: This study demonstrated a significant association between the SCN1A (3184 AG and GG) and SCN2A (56GA and AA) genotype with CBZ-nonresponsive epilepsy.

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). Effects of the current statins were studied on spontaneous activity of isolated rabbits’ jejunal preparations. Different molar concentrations (10−12–10−2M) 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. 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. 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.

Ethnicity variation is one of the main factors that may affect drug response in clinical practice. As MTHFR gene affects different transcriptome and proteome which affect the clinical response of drugs. Purpose of the current study was to observe possible variations in plasma levels of carbamazepine monotherapy and seizures’ control in Pakhtun population of Khyber Pakhtunkhwa (KP) in the context of MTHFR (C677T and A1298C) gene polymorphisms. Blood was collected from the epileptic patients treated with carbamazepine monotherapy for the first time following respective oral doses on its steady state concentration after 3 h of morning dose at 3rd and 6th month of the therapy. Plasma carbamazepine levels were determined using reverse phase high performance liquid chromatography after method validation. MTHFR (C677T, AA298C) gene was genotyped. Patients were followed on 3rd and 6th month of the therapy for monitoring of response to carbamazepine therapy. Following for 3rd and 6th month of duration of carbamazepine therapy, poor seizure controlled patients were more likely noticed in heterozygous variants (677CT and 1298 AC) of MTHFR gene (P < 0.05). There was no significant (P > 0.05) difference in the dose and plasma level of carbamazepine among different genotypes of MTHFR (C677T and A1298C) gene. Similarly, the difference in dose and plasma level of carbamazepine was not significant (P > 0.05) in the responder and non-responder people with epilepsy. Our study suggests that heterozygous variants of MTHFR (C677T and A1298C) gene are associated with poor seizure control in Pakhtun population of KP despite the fact that plasma level of carbamazepine were found within the therapeutic range.