Technological Innovation in Pharmaceutical Research Vol. 10

Objective: Anabolic androgenic steroids (AAS) are synthetic derivatives of the male sex hormone testosterone. In the present investigation, we studied the impact of one of the AAS compounds 17\(\alpha\)-methyltestosterone on acethylcholinesterase (AChE) enzyme activity in different parts of mice brain viz. forebrain, hippocampus, midbrain, and hindbrain.

Methods: The adult female mice were assigned to four experimental groups to which different doses of 17\(\alpha\)-Methyltestosterone (17\(\alpha\)-MT- 0.5, 5.0 and 7.5 mg/kg bwt, respectively) were administrated s.c. for 30 days.

Results: A significant increase in AChE activity in forebrain and midbrain (low and medium dose treatment) suggests a reduction of cholinergic neurotransmission efficiency due to a decrease in acetylcholine levels in the trans-synaptic cleft. Further, a concurrent reduction in AChE activity was observed in the whole brain, hippocampus and hindbrain of 17\(\alpha\)-MT treated mice suggest the impairment in neuronal transmission. Since the regulation of cholinergic system through acetylcholine hydrolysis has been largely attributed to AChE activity, a significant reduction in its activity may lead to stress-related anxiety, memory loss with some cognitive and behavioral aspects in the mice.

Conclusion: Based on the observed results we propose that 17\(\alpha\)-MT an alkylated steroid compound has a negative impact on AChE enzyme activity in different parts of mice brain leading to impairment in neuronal transmission.

In Indian medicine, Argyreia speciosa is a highly effective medicinal plant.It has traditionally been used to treat a variety of human ailments and disorders. The antifungal activity of aqueous, ethanolic, chloroform, and petroleum ether extracts of A. speciosa against Candila albicans was investigated in this study. The ethanolic extract and petroleum ether extract were shown to have high activity against the tested fungal strain, whereas the aqueous extract had very little activity and the chloroform extract had no activity. Ethanolic extract showed the potent antifungal activity as compared to other extract and the Zone of inhibition of test drug is compared to standard.

Objective: To study the hepatoprotective effect of aqueous extract of Vernonia amygdalina on acetaminophen-induced liver damage in abino wistar rats.

Methods: Twenty five (25) albino rats weighing (120±20 g) were randomly divided into five (5) groups with five (5) rats per group. Group A served as normal control and received no treatment. Group B received only a single dose of acetaminophen (750 mg/kg, i.p) and served as negative control . Group C served as positive control and received Vitamin C (200 mg/kg, oral)  for 2 weeks, while  Group D and E served as the test groups and received aqueous bitter leaf extract; high dose (500mg/kg,oral) and low dose (250mg/kg, oral) separately for 2 weeks following acetaminophen challenge.

Results: The administration of single dose of acetaminophen (750 mg/kg, i.p) resulted in liver damage with AST, ALT and ALP levels: 48.33±10.14U/L, 60.00±13.23U/L and 229.67±23.38U/L respectively. The treatment with bitter leaf resulted in a reversal of the acetaminophen-induced liver damage with AST, ALT and ALP levels: 20.67±1.76U/L (P<0.05), 16.67±3.52U/L (P<0.01) and 131.67±7.27U/L (P<0.01) respectively when compared with acetaminophen alone. Histopathological results also showed minor or non significant hepatocellular damage in the test groups; hence hepatoprotection by Vernonia amygdalina.

Conclusion: The aqueous extract of Vernonia amygdalina possesses hepatoprotective properties against acetaminophen-induced liver damage.

Introduction: It has been extensively reported that drug-overdose is the leading cause of liver injury in the world today. Diets rich in natural antioxidants have been observed to offer substantial remedy to drug-induced organ injuries.

Objective: The aim of this study was to investigate the hepatoprotective effects of tomato extract against Acetaminophen-induced acute hepatotoxicity in rats.

Methods: Phytochemical analyses were performed. A total of 24 albino rats weighing (110±10 g) were randomly allocated to four groups (A-D), with six rats per group. Group A was the normal control and received no treatment. Group B was the negative control and received a single dose of acetaminophen (750 mg/kg, i.p) only. Group C served as test group and received a single dose of acetaminophen (750 mg/kg, i.p.) before treatment with tomato extract (30 mg/kg, oral) for 14 consecutive days. Group D received simultaneous administration of tomato extract (30 mg/kg, oral) and acetaminophen (750 mg/kg, i.p) for 14days.

Results: The single dose of Acetaminophen caused liver cell injuries with significant increase in the levels of the liver enzymes: AST (67.67±11.41U/L); ALT (46.33±10.59U/L) and ALP (223.70±23.31U/L) in rats in negative control when compared with normal (p<0.05 or p<0.01). The daily administration of the tomato extract was able to attenuate the acetaminophen-induced hepatotoxicity on the liver enzyme marker levels: In Group C: AST (23.00± 3.61U/L, P<0.01); ALT (17.67± 3.48U/L, P<0.05) and ALP (121.30±8.11U/L, P<0.01). In Group D, AST (26.67±2.91U/L, P<0.01); ALT (18.67±1.76 U/L, P<0.05) and ALP (124.72±9.33U/L, P<0.01) when compared with negative control group. The histological results also revealed no significant liver injury in the groups that received tomato extract when compared with the normal control.

Conclusion: Tomato extract possesses hepatoprotective ability against acetaminophen-induced liver injury.

This experimental studies showed that its active components [10]-gingerol exert anti-diabetic effects against streptozotocin (STZ) and high-fat-diet (HFD) -induced diabetic rats. The occurrence of type 2 diabetes mellitus is rapidly rising around the world’s population. India is the ‘diabetes capital of the world’ with 62.4 million Indians having type 2 diabetes. The current treatment for type 2 diabetes includes insulin and oral hypoglycemic drugs i.e. sulfonylurea derivatives, thiazolidinediones, biguanides and \(\alpha\)-glucosidase inhibitors but these medications have most of the side effects. Wistar rats (150-200 g) were group housed (n=6) under a standard 12 h light/dark cycle and controlled conditions of temperature and humidity (25±2°C, 55–65%). The histopathological illustration showed normal acini and normal cellular population in the islets of Langerhans in the pancreas of vehicle-treated rats. Our study suggested that [10]-gingerol dose-dependently produced antidiabetic activity. In this study might be helpful to understand the role of [10]-gingerol in the clinical treatment of diabetes mellitus.

Introduction: Type 2 diabetes mellitus is one of the most common non- communicable diseases associated with short term and long term complications.

Material and Methods: A total of 60 patients were included in the study divided into 2 groups of 30 patients each. Group 1 patients were given Teneligliptin 10 mg once a day and metformin 500 mg twice a day after meals for 12 weeks. Group 2 patients were given Glimepiride 1 mg once a day and metformin 500 mg twice a day after meals for 12 weeks. After the written consent, history, clinical examination, biochemical investigations including FBG, PPBG, HbA1c and lipid profile were done. Repeat FBG and PPBG were done every week upto 12 weeks. HbA1c and lipid profile were done at the beginning and at the end of study.

Results: Change in FBG was more in group 1 as compared to group 2. On comparison of reduction in change in PPBG in patients of group 1 versus group 2, there was a highly significant reduction in group 1. Change in HbA1c, total cholesterol levels, triglyceride levels, HDL and LDL was more in group 1 than in group 2.

Conclusion: Teneligliptin and metformin caused a greater improvement in glycaemic and lipid profile as compared to Glimepiride and metformin. Thus teneligliptin is more efficacious than glimepiride.

Poison is a substance that is harmful to the living organisms in all respects. It can even cause immediate death of the exposed. Ayurvedic authors mention one terminology "BISHA" that has close similarity with "POISON" mentioned in the modern toxicology. A vivid description of Bisha is available in the Ayurvedic classics starting from definition, classification, properties, mode of action, signs and symptoms, treatment etc. The discussion on the route of entry and media through which poison can be given to a targetted human / animal is also attractive. The Ayurvedic authors also have given guidance to the Toxicologists (Bishavaidya) on the procedures of prognostitization of a patient of poisoning. Each and every principle of the Ayurvedic scholars needs study and evaluation through the modern techniques to make the modern socity convinced .  

Background: Intensive Care Unit is used to treat patients closer to their beds, in order to observe them more as distinct people to almost all the critically-ill patients.

Aims: The present study analyze the outcome of the prophylactic measures has been taken to prevent risk of stress ulcer, Urinary tract infection, pressure ulcer and chest infection in the ICU’s admitted acutely ill Critical Patients.

Methods: One hundred admitted patients in the ICU, 25 each sets of the patients observed their prophylactic management to prevent stress ulcer, pressure ulcer, UTI and chest infection, observations noted for the 7 days, directly by seeing and by cross-checked patient’s case-sheets.

Results: There were 2 (8%) patients developed stress ulcer, 1 (4%) Catheter

associated bacteriuria, 2 (8%) patients grade II pressure ulcer, and 5 (20%) patient’s done endotracheal intubation. All these 5 (20%) report of sputum culture found Ps. Aeruginosa, Klebsiella sensitive for Ceftriaxone + Sulbactum. The standard nursing care done by the on duty nursing staffs, i.e., no one given Ryle’s tube feeding for the stress ulcer cases, advised soft, palatable, non-spicy oral diet, Pressure ulcer’s 8% patients shifted on the air-bed mattress, ulcer’s cleaned with normal water soaked soft-napkin and applied sterile pad compressed dressing locally. For the ventilator in-situ patient’s, endotracheal tube cleaned 8-12 times within 12 hours. The Inbuilt Ventilator tube cleaned, and its filter changed and kept ready by the following standard aseptic precaution before using the ventilator. The chest physiotherapy was done by the chest medicine specialist of the all 5 ventilated patients. Prophylactic medication provided, i.e., Injection Pantoprazole 40mg once daily, Injection Ciprofloxacin 400mg twice daily, and Injection Inj. Ceftriaxone + Sulbactum gm 12 hourly interval administered daily.

Conclusions: Standard nursing care was prime intervention as an Intensive Care Unit Prophylaxis along with Injection Pantoprazole 40mg once daily provided to prevent stress ulcer. Injection Ciprofloxacin 400mg twice daily provided to prevent Catheter Associated Bacteriuria. Injection Ceftriaxone + Sulbactum 1gm 12 hourly provided to prevent Ventilator Associate Pneumonia and pressure ulcer. Injection Ceftriaxone + Sulbactum 1gm 12 hourly interval. Intensive Care Unit’s Prophylactic measures helped to prevent further complication and reduced morbidity.

Due to the irrational use of drugs, we are facing numerous problems of overuse, misuse, increased cost, antibiotic resistance etc. The present study was conducted in a tertiary hospital in which the patients are referred from surrounding rural and tribal areas. It is a retrospective study that included the patients admitted in clinical departments. A total of 200 patients (Males 41.5% and Females 58.5%) were included and their case records were reviewed. Most of the patients belong to age group < 30 years. The average No. of drugs per prescription was 4.76.Intravenous route was commonly used. The dose of the drug was inappropriate in 38% patients and inappropriate frequency in 3% cases. It was found that the most commonly prescribed group of drugs was antimicrobial agents (41.53%) with Ampicillin (53.01%) as the most commonly prescribed antimicrobial agent. Culture and Sensitivity was not conducted in any of the patient. Single antimicrobial agent was prescribed in 42% cases and combination of 2 antimicrobial agents in 38% cases. Thus, the drug utilisation in patients included in the study is not rational and hence, many recommendations were suggested. 

Beans are one of the world's most consumed and widely grown vegetable crops, but their yield is hampered by a variety of diseases caused by whiteflies and other insects.Whiteflies can also spread a variety of viral diseases to beans. Bean Common Mosaic Virus (BCMV), Bean Yellow Mosaic Virus (BYMV), Bean Golden Mosaic Virus (BGMV) etc. A variety of synthetic pesticides have been used in agriculture to control insects, which damage the plant and have a negative impact on the environment; however, their negative impact on the environment necessitates the use of more environmentally friendly methods for pest management. This paper discusses the synthesis, physicochemical characterization, and application of a mixture of potassium palmitate and pyrethroids; pyrethroids, and potassium stearate as non- persistent insecticides against whiteflies found on bean plants, as well as the use of the T-test to compare the efficacy of prepared insecticidal formulations.

Due to their synthetic utility and extensive variety of pharmacological effects, indole and benzimidazole, as well as their substituted derivatives, help to draw interest. The N-substituted fused heterocyclic compounds are usually physiologically active and could be employed as antitumor medicines. The various reactions reported that reactions of K2CO3 showing its essentiality for a particular reaction due to its characteristics like solubility in water, mild base character, easy availability, eco-friendly, and nontoxic in nature. In the presence and absence of phase transfer catalyst such as PEG-400 and TEBAC, the effect of the ratio of catalyst used anhydrous K2CO3 for its N-1 alkylation or arylation of indole-3-carboxaldehyde and 2-acetylbenzimidazole is observed. The ratio 1:4 of anhydrous K2CO3 along with PEG-400 gives, ease of catalyst handling, mild reaction conditions and reactions carried out at 10-15ºC temperature with excellent yields. The simplicity of the approach makes it attractive for the synthesis of N-fused heterocyclic derivatives that could be employed as biological substitutes.

Since discovering new chemical entities is a complex, expensive, and time-consuming process, current trends have shifted toward designing and developing improved drug delivery methods for existing drugs. Recent times, fast dissolving oral films were introduced to the market, attracting the attention of a large number of pharmaceutical companies due to their numerous advantages over other oral dosage forms, including ease of administration, better patient compliance, rapid drug absorption, and rapid onset of action with instant bioavailability. Aside from these advantages, quick dissolving oral films can be employed in children, the geriatric, and bedridden patients who have difficulties swallowing tablets or capsules. Initially, fast-dissolving oral films of breath strips, confectionary, and oral care treatments were developed, but it has now evolved into an innovative and widely accepted technique for delivering both OTC and prescription drugs.  Fast dissolving films are gaining interest as an alternative to fast dissolving tablets. The films are designed to disintegrate in a matter of seconds when they come into touch with a wet surface, such as the tongue, allowing the user to eat the food without the need for extra liquid. This ease of use gives a marketing benefit as well as greater patient compliance. Since the medicine is absorbed straight into the systemic circulation, it avoids gastrointestinal degradation and the first-pass impact.Solvent casting is used to make the Loperamide hydrochloride mouth dissolving film. The ingredient used for formulation Loperamide hydrochloride as a Anti-Diarrheal, HPMC-E50, HPMC-E15-LV and PVA as film forming polymer, propylene glycol as a plasticizer, Sodium starch glycolate (2-8%) as super disintegrant, lemon oil (2-5%) as a flavoring agent, citric acid (2-6%) as a Saliva Stimulating Agent, methylparaben (0.015%) as a preservative. Tensile strength, disintegration time, and percentage drug dissolution were chosen as independent variables, whereas tensile strength, disintegration time, and percentage drug dissolution were chosen as response variables. Mass uniformity, thickness, percent drug content, folding endurance, surface pH, moisture uptake, % swelling, percentage elongation, tensile strength, in vitro disintegration time, and in vitro percentage drug dissolution were all considered when evaluating the formulations. Loperamide was discovered to be a viable candidate for development of Fast Mouth Dissolving Films. The solvent casting procedure used to create Loperamide oral films is simple and cost-effective. It was deemed acceptable by the super disintegrants who were used in this study. FT-IR tests of drug-excipient compatibility indicated no physicochemical interaction. The obtained oral films were clear, had sufficient physical strength, and had a suitable disintegration time. In vitro dissolution experiments of all formulations revealed a superior release profile than pure medicines.Based on the test results, it was determined that film formulation F7, which contains a blend of HPMC E15 and PVA film formers, is the best formulation among the others..

Epilepsy in children is a complex disease, with a variety of distinct syndromes and many alternative treatment options. Even with a plethora of available treatment options, childhood epilepsies are commonly associated with seizures that are resistant to existing treatment methods. Treatment of pediatric epilepsy is challenging and requires more effective therapy to avoid short-term and long-term neurological disorders. Marijuana has been used to treat disease since ancient times. Marijuana ingredients Cannabidiol (CBD) and D9-Tetrahydrocannabinol (THC) have created a significant research interest as potential therapy options in epilepsy treatment. THC is the major psychoactive component of marijuana that aids in reducing epileptic seizures. CBD has proven to have anticonvulsant effect not only in experimental models but also in clinical studies. Research studies have provided strong evidence for safety and anticonvulsant properties of medical marijuana. Principal concerns regarding the use of medical marijuana in children include lack of standardization and regulation, imprecise dosing, possible adverse side effects and medication interactions.

Leaves of Lantana camara were freshly harvested, dried in the shade and pounded. Obtained leaf powder (2g) L. camara was cold extracted with 3 x 40-ml MeCN. Purification of the extract went through thin layer chromatography, column chromatography, preparative thin layer chromatography and fractional crystallization. Pooled fractions that contained bio constituent of latandene B as shown on thin layer chromatography were taken for HPLC analysis after being dissolved in HPLC grade methanol. Aliquots (20 µl) were taken for HPLC analysis. The HPLC system used was from Waters (USA) with 510 pump, Rheodyne injector with a 20-µl loop, 490E multichannel detector and Millennium 2010 dataprocessor. The detector was set at 210 nm. Purified and spectroscopic determined lantadene B content of young and matured leaves of L. camara was 347.0 ± 3.0 and 522.3 ± 37.1. Identified Lantadene B was screened against Trypanosoma evansi for trypanocidal activity on Vero cells grown in Dulbecco's Modified Eagle Medium (DMEM) and supplemented with foetal calf serum (FCS) 20-40% at appropriate conditions. In vitro cytotoxicity test of lantadene B at concentrations (1.56-100 µg ml-1) was done on Vero cells but without FCS. In vitro trypanocidal activity varied from immobilization, reduction and to the killing of trypanosomes in corresponding ELISA plate wells. At 250 µg ml-1of purified Lantadene B, there was drastic reduction of average mean trypanosomes count (40.±0.0 to 1.667±0.33) was observed. At 500 µg ml-1 of the test lantadene B, there was complete killing of trypanosomes (40.±0.0 to 0.00±0.00) at 8 h of incubation, which was statistically the same as diminazine aceturate (50 µg ml-1) at 4 h. Trypanosomes counts decreased in concentration and time –dependent manner with significant difference (P \(\le\) 0.05 to 0. 01)). During in vitro cytotoxicity test, Purified lantadene B and diminazine aceturate standard drug, were cytotoxic to Vero cells at all concentrations except at concentrations of 6.25-1.56 µg ml-1. Lantadene B and diminazine aceturate were cytotoxic to Vero cells at the same concentration. Lantadene B was responsible for higher anti-trypanosomal activity, which could be a future candidate compound for a new trypanocide.

In our ongoing research to determine the presence of antitrypanosomal compound(s) from medicinal plant, leaves of Parkia biglobosa were extracted with methanolic solvent at concentrations (250-1000 µg ml-1). Methanolic plant extract (MPE) obtained was tested against Trypanosoma evansi for trypanocidal activity. This was performed on Vero cells grown in Dulbecco's Modified Eagle Medium (DMEM) and supplemented with foetal calf serum (FCS) 20-40% at appropriate conditions. In vitro cytotoxicity test of P. biglobosa methanolic leaf extract at concentrations (1.56-100 µg ml-1) was done on Vero cells but without FCS. In vitro trypanocidal activity varied from immobilization, reduction and to the killing of trypanosomes in corresponding ELISA plate wells. At 250 µg ml-1of MPE of P. biglobosa, there was drastic reduction of average mean trypanosomes count in the extract (40.±0.0 to 7.000±0.33) as observed. At 500 µg ml-1 of the test extract of P. biglobosa, there was complete killing of trypanosomes (40.±0.0 to 0.00±0.00) at 9 h of incubation, which was statistically the same as diminazine aceturate (50 µg ml-1) at 4 h. Trypanosomes counts decreased in concentration and time –dependent manner with significant difference (P \(\le\) 0.05 to 0. 01)). MPE of P, biglobosa and diminazine aceturate, standard drug, were cytotoxic to Vero cells except at concentrations of 12.5- 1.56 µg ml-1. Alkaloids, flavonoids, anthraquinones, tannins, phlobotannins and cardiac glycoside already isolated from P. biglobosa leaves and other parts of it could be responsible for higher antitrypanosmal activity.

Ageratum houstonianum leaves are a common poisonous weeds found on the vast valley of Kangra in Palampur, Himachal Pradesh State, India. Freshly harvested leaves sample of Ageratum houstonionum were dried under shade and powdered. Leaf sample of A. houstonionum was extracted by process of hydrodistillation using a Clevenger-type apparatus for the preparation of essential oil. Extract from A. houstonianum was prepared by dissolving 5 µL of the essential oil in 10 mL methanol. All the sample was filtered through a Whatman (Maidstone, England) stainless steel syringe assembly using a 0.22 µm Durapore (Millipore: Milford, USA) membrane filter. Purification processes via column chromatography, thin layer chromatography and preparative thin layer chromatography were done. Reverse phase HPLC analysis was carried out via a Waters HPLC system consisting of model 510 and 515 pumps, a Rheodyne injector, a Novapak C₁₈ column (250 x 4.6 mm i.d.; 4 µm), a model 490E multi-channel detector and Millennium 2010 sata manager. The mobile phase constituents were filtered using a Durapore 0.22 µm membrane filter. The elution was carried out with a linear gradient of acetonitrile: water (40:60) to pure acetonitrile in 60 min at a flow rate of 1 mL/min. detection was at 210, 240, 280 and 320 nm. The precocene was eluted within 25 min, the peak areas showed good reproducibility (average relative standard deviation were 0.78%), and the calibration curves (i.e. mass of precocene standard injected vs. peak area detected at 210 nm) were linear over the range of 0.05-10 µg (for precocene I, y = 6654454 x + 176626, r² = 0.99 and for precocene II, y = 4618457 x + 133472, r² = 0.99). Standard sample containing precocene I (1 mg/mL) and precocene II (1 mg/mL) obtained from Sigma (St Louis, MO, USA) were prepared in methanol. Identified precocene I was screened against Trypanosoma evansi for trypanocidal activity on Vero cells grown in Dulbecco's Modified Eagle Medium (DMEM) and supplemented with foetal calf serum (FCS) 20-40% at appropriate conditions. In vitro cytotoxicity test of precocene I at concentrations (1.56-100 µg ml-1) was done on Vero cells but without FCS. In vitro trypanocidal activity varied from immobilization, reduction and to the killing of trypanosomes in corresponding ELISA plate wells. At 250 µg ml-1of purified precocene I, there was drastic reduction of average mean trypanosomes count to complete killing of trypanosomes (40.±0.0 to 0.00±0.00) at 9 h of incubation, which was statistically the same as diminazine aceturate (50 µg ml-1) at 4 h. Trypanosomes counts decreased in concentration and time –dependent manner with significant difference (P \(\le\) 0.05 to 0. 01)). During in vitro cytotoxicity test, Purified precocene I and diminazine aceturate standard drug, were cytotoxic to Vero cells at all concentrations except at concentrations of 6.25-1.56 µg ml-1 and 1.56 µg ml-1, respectively. Precocene I was responsible for higher anti-trypanosomal activity. Precocene I could be near future trypanocidal compound for a new trypanocide. To attest its full and firm trypanocidal activity potential, in vivo test need to be conducted alongside the in vitro method.