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  • Volume 9, Issue 1
    Research Article
    Julekha Khatun*, Arif Hosen MM, Ashim Kumar Ghosh, Rawshan Ara Khatun, and Shish Mohammad Sarkar
    Background: Neoadjuvant chemotherapy is an innovative approach that has got significant attention for treating breast cancer. Optimal management of locally advanced breast cancer (LSBC), generally includes a combination of neoadjuvant chemotherapy followed by surgery, local radiotherapy and adjuvant chemotherapy with or without hormone therapy.
    Methodology: Our study was carried out on histopathologically confirmed 60 locally advanced breast cancer patient [tumor > 5cm in diameter (T3), with mobile or fixed nodes (N1-2), OR associated with involvement of skin or chest wall (T4), OR with fixed axillary nodes or ipsilateral Supraclavicular nodes] were enlisted and were divided into two study groups. Arm-A consisting of 30 patients were treated with Adriamycin 60 mg/m2 and Cyclophosphamide 600 mg/m2 (AC), & Arm-B consisting of 30 patients were treated with Adriamycin 50 mg/m2 and Docetaxel 75 mg/m2 (AD), 4 cycle 3 weeks interval.
    Results: The study was designed to compare the response of neoadjuvant chemotherapy with Adriamycin and Cyclophosphamide versus Adriamycin and Docetaxel in locally advanced breast cancer. As the result of the study, baseline characteristics were almost similar between the two arms. In Arm-A clinical complete response (CR), was achieved in 05 patients (16.7%), and clinical partial response (PR), was 18 patients (60%). In Arm-B clinical complete response (CR), was achieved in 08 patients (26.7%), and clinical partial response (PR), was 19 patients (63.3%). Overall clinical response (complete & partial), in Arm-A & Arm-B was 76.7% versus 90%. After 4 cycle chemotherapy, 23 patients in Arm-A and 27 patients in Arm-B underwent a modified radical mastectomy. Among them, pathological complete response (CR), was found in 02 patients (8.7%), in Arm-A and 04 patients (14.9%), in Arm-B. Hematological toxicities especially grade-3 anemia & neutropenia were more in Arm-B than Arm-A, but no patient develop grade-3 thrombocytopenia. Among non-hematologic toxicities, grade-3 nausea vomiting was more in Arm-A but alopecia and neuropathy were more in Arm-B. All these toxicities were managed by symptomatic management.
    Conclusion: The overall clinical and pathological response was found greater in Arm-B but not statistically significant. Both hematologic and non-hematological toxicities were a little bit more in Arm-B specifically grade-3 neutropenia, except the incidence of nausea and vomiting was more in Arm-A but those were acceptable and manageable.
    Enes Seyda Sahiner* and Ali Akcay
    Objective: The aim of this study was to examine the relationship between obestatin and malnutrition in patients with chronic renal failure (CRF).
    Method: The study included 43 hemodialysis patients with chronic renal failure aged >18 years and 43 healthy matched controls.
    Results: CRF patients and healthy controls were not significantly different in terms of obestatin levels. For all subjects, obestatin was positively correlated with body fat, waist circumference, Mini Nutritional Assessment score, body mass index, triglycerides, and low-density lipoprotein levels. Regression analysis showed that body fat was a determinant of obestatin.
    Conclusion: In reference to our results, we conclude that obestatin is a marker associated with obesity and was not significantly different between patients with CRF and healthy controls.
    Review Article
    Roy G Beran*
    Introduction: Carbamazepine (Tegretol®) (CBZ), has been available for half a century suggesting all that needs to be said has been said but it has truly withstood the test of time.
    History revisited: CBZ was discovered during the research and development of imipramine, a tricyclic antidepressant and retains psychotropic benefits which are propitious in the treatment of epilepsy. CBZ has both standard antiseizure medication (ASM), adverse events (AEs), as well as idiosyncratic AEs that must be appreciated when using CBZ. Genotyping allows definition of those for whom CBZ is contra indicated. It can also exacerbate certain seizure types, such as generalised epilepsies, such as juvenile myoclonic epilepsy.
    Risk/Benefit Ratio: Blood level monitoring of CBZ levels allows tailoring of treatment to the patient’s needs and identifies both ASM causing toxicity or non-compliance/non-adherence, possibly before breakthrough seizures occur. Medication interactions, consequent to liver enzyme induction, need to be acknowledged and monitored.
    Conclusion: It follows that with adequate preparation and understanding, CBZ remains a favoured ASM in the treatment of focal epilepsy. As with any medication it is imperative to understand the ‘pros and cons’ but, with due diligence, CBZ deserves to remain at the top of the list for quite some time to come.
    Gary F. Merrill*
    We live in an increasingly dangerous and uncertain world. Part of the danger and uncertainty stems from the costs and high rates of turnover of new drugs created by ‘profit margins’ within big pharmaceuticals and the biotechnology sectors (e.g. coronavirus vaccinations). The elderly and poor are frequently in the dark about the efficacy, legitimacy and safety of the drugs they are prescribed (personal communication). Some think they have to choose between buying groceries, paying property taxes, or losing health because they can’t afford their prescription medications. This is a shameful and unfortunate price to pay in exchange for the greed and indifference of profiteers.
    Gian Maria Pacifici*
    Cefotaxime is active against Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Citrobacter, Enterobacter, Serratia, Neisseria gonorrhoea, Staphylococcus aureus and Streptococcus pneumoniae. Cefotaxime cured the meningitis caused by Haemophilus influenzae, penicillin-sensitive Streptococcus pneumoniae, and Neisseria meningitides. The drug is metabolized in-vivo to desacetylcefotaxime and desacetylcefotaxime is converted into 3-desacetylcefotaxime lactone. Cefotaxime is administered intravenously and the dose is 50 mg/kg given twice-daily, thrice-daily, and 4 times-daily in infants with a postnatal age of 1 week, 2 to 3 weeks and > 3 weeks, respectively, and it is 50 mg/kg thrice-daily in children. The elimination half-life of cefotaxime ranges from 3 to 5 hours in infants and it is about 0.8 hours in children. The total body clearance of cefotaxime ranges from 0.1 to 0.3 L/h/kg in infants, it is 0.11 and 0.74 L/h/kg in two children, and the renal clearance is lower than the total body clearance. The total body clearance of desacetylcefotaxime is about 0.36 L/h/kg. Cefotaxime distribution volume is lower than the water volume in both infants and children. This drug interacts with drugs; the interaction may cause inhibitory or synergistic effects and the treatment with cefotaxime has been extensively studied in infants and children. Cefotaxime penetrates into the cerebrospinal fluid and the cerebrospinal fluid to serum ratio ranges from 10 to 26% for cefotaxime and from 21 to 29% for desacetylcefotaxime. Cefotaxime is transferred across the human placenta and the umbilical cord to maternal blood ratio is 77% for cefotaxime and 99% for desacetylcefotaxime. Cefotaxime migrates into the breast-milk in significant amounts. The aim of this study is to review the dosing, efficacy and safety, metabolism, pharmacokinetics, drug-interactions, treatment, meningitis, penetration into the cerebrospinal of cefotaxime in infants and children, and the cefotaxime transfer across the human placenta and migration into the breast-milk.
    Original Article
    Mulugeta Russom*, Filipos Yohannes, Abel Tekle, Ruth Ghirmay
    Introduction: Ibuprofen was associated with hypoglycemia in a single published case report in a diabetic patient. Ibuprofen, however, has never been associated so far with hypoglycemia in previously healthy non-diabetic individuals and thus, it is not listed as adverse effect in its summary of product characteristics approved by major regulatory authorities.
    Objective: This study was conducted to assess the causal relationship between ibuprofen and hypoglycemia in diabetic and non-diabetic individuals.
    Materials and Methods: Analysis of the literature and the WHO global database of individual case safety reports, VigiBase, was made to explore evidence on the association of ibuprofen and hypoglycemia. The unpublished data and the currently availablepublished toxicological, biological, clinical and epidemiological evidence, if any, was systematically organized using Austin Bradford Hill criteria, causality assessment framework, to assess the causal link between ibuprofen and hypoglycemia.
    Results: In VigiBase, there were 125 cases of hypoglycemia associated with ibuprofen, reported from 19 countries. About 50% had history of diabetes. Ibuprofen was reported as sole suspect in 36.8% of the cases and the only drug administered in18.4%. Hypoglycemia resolved following discontinuation of ibuprofen in 21.6% and recurred in three patients with rechallenge. Outcome was fatal in 10.5%. Where ibuprofen was solely administered, median time-to-onset of hypoglycemia was one-day following administration of the drug. In an experimental study, a significant decrease in blood glucose level was observed at a higher dose of ibuprofen compared to a low-dose.
    Conclusion: Currently available totality of evidence reflects a possible causal association between ibuprofen and hypoglycemia that need to be substantiated with further studies.
    Review Article
    Amit Joshi1 and Vikas Kaushik*
    Computational techniques in drug discovery and vaccine prediction basically revolve around molecular docking to retrieve perfect interaction models for ligand and receptor. Binding energies can be obtained for perfectly interacting complexes. Many tools like DINC, PatchDock-Firedock, and AutoDock-Vina are deployed to conduct molecular docking in various pipelines. Discovering drug and vaccine becomes facile due to use of advanced docking techniques. Also allow researchers to screen out possible models of interaction on the basis of atomic contact energy, binding energy, and global energy. This review article provides insights to use efficient approach for docking related investigations.
    Gian Maria Pacifici*
    Captopril is a potent angiotensin-converting enzyme inhibitor with a Ki of 1.7 nM. Captopril may be administered orally or intravenously and the oral bioavailability is about 75%. Most of the drug is eliminated in urine, 40 to 50% as captopril, and the rest as captopril disulphide dimers and captopril-cysteine disulphide. Captopril may be used in the treatment of congestive cardiac failure, and in moderate to severe hypertension in infants and children. The oral test dose of captopril is 10, 10 to 50, or 100 µg/kg thrice-daily in preterm infants, term infants, and older infants, respectively, and in children the oral test dose is 100 to 300 µg/kg twice-daily or thrice-daily. Captopril has been found efficacy and safe in treating heart failure in infant and in reducing hypertension in infants and children. The effects of captopril are: reduction of blood pressure, decrease pulmonary-to-systemic blood flow ratio, decrease systemic vascular resistance, and reduce aldosterone and natriuretic peptide blood concentrations in infants and children. Captopril causes different adverse-effects. The elimination of captopril is about 3 hours in infants and children. Captopril interacts with allopurinol, carnosine, potassium-sparing diuretics, or verapamil. Captopril treats infantile haemangioma, is a systemic vasodilator and reduces the blood pressure in hypertensive infants and children, and captopril poorly migrates into the breast-milk. The aim of this study is to review the published data of captopril dosing, efficacy and safety, effects, adverse-effect, pharmacokinetics, interaction with drugs, and treatments in infants and children, and the migration of captopril into the breast-milk.
    Gian Maria Pacifici*
    Phenytoin is effective against all types of focal and tonic-clonic seizures but not absence seizures. In infants, the status epilepticus is treated with phenytoin intravenous loading dose 20 mg/kg followed by a maintenance dose of 2 mg/kg twice-daily or thrice-daily. In children, the treatment of tonic-clonic seizures is carried out with oral phenytoin and the status epilepticus is treated with intravenous phenytoin and in both treatments phenytoin dose varies according to the child age. Phenytoin is hydrolysed into hydroxyphenytoin and also a phenytoin catechol derivative is formed, the catalysts are several CYPs, and p-hydroxyphenytoin is conjugated with glucuronic acid. Phenytoin elimination half-life is 20.7 and 15.1 hours in newborns and infants, respectively, and in diseased children, aged 9 months to 13 years, phenytoin was co-administered with chloramphenicol or cefotaxime and phenytoin half-life is 23.7 and 15.4 hours when phenytoin is co-administered with chloramphenicol or cefotaxime, respectively. The treatment and trials with phenytoin have been extensively studied in infants and children and phenytoin interacts with drugs. Phenytoin penetrates into the cerebrospinal fluid and is transported into the human brain in significant amounts. Phenytoin freely crosses the human placenta and migrates into the breast-milk where achieves concentrations of few µg/ml. The aim of this study is to review the published data of phenytoin dosing, pharmacokinetics, treatment, and trials in infants and children, and phenytoin metabolism, interaction with drugs, penetration into the cerebrospinal fluid, transport into the human brain, placental transfer, and migration into the beast-milk.
    Review Article
    Gian Maria Pacifici*
    Histamine H2 receptor antagonists inhibit acid production by reversibly competing with histamine for binding to H2 receptors on the basolateral membrane of parietal cells. Four H2 receptor antagonists are available: cimetidine, ranitidine, famotidine, and nizatidine. The major therapeutic indications for H2 receptor antagonists are to promote healing of gastric and duodenal ulcers, to treat uncomplicated gastroesophageal reflux disease, and to prevent the occurrence of stress ulcers. The H2 receptor antagonists generally are well tolerated with a low incidence of adverse-effects. Ranitidine may be administered orally or intravenously and following oral dosing it is rapidly absorbed. In newborns, the oral dose of ranitidine is 2 mg/kg thrice-daily and in older infants it is 2 to 4 mg/kg twice-daily. In children, the ranitidine dose varies according to the child age. Ranitidine causes different effects in infants and children. Ranitidine is converted into ranitidine N-oxide, ranitidine S-oxide, and desmethyl ranitidine, and the former metabolite is the major metabolite. The pharmacokinetics of ranitidine have been studied in infants and children and the elimination half-life is 2.79 hours in infants and 2.03 hours in children. Ranitidine interacts with drugs and the treatment of infants and children with ranitidine has been extensively studied. Ranitidine freely crosses the human placenta and migrates into the breast-milk in significant amounts. The aim of this study is to review the ranitidine dosing, effects, pharmacokinetics, and treatment in infants and children, and ranitidine metabolism, drug interaction, placental transfer and migration into the breast-milk.
    David Calderón Guzmán, Armando Valenzuela Peraza, Hugo Juárez Olguín*, Mónica Punzo Soto, and Francisca Trujillo Jiménez
    Insulin is the most effective pharmacological treatment for the control of hyperglycemia. The liver is the main target tissue for the action of insulin and insulin resistant liver can lead to hyper-insulinemia and eventually hyperglycemia. The receptors of insulin and their downstream pathways are extensively distributed in the brain. These receptors play crucial roles in the regulation of different central nervous system tasks. Therefore, dysfunction at different levels of insulin signaling and metabolism can contribute to the development of a bunch of clinical disorders.
    Recent studies have detected that many bioactive compounds, derived from plants; have an array of beneficial functions and could be important sources of potential novel therapies for chronic diseases and for attenuating symptoms related with diabetes, especially oxidative stress and inflammation. The precise molecular mechanisms by which the dysfunction of insulin signaling and metabolism induce these health problems are not yet clear. Hence, the aim of this work was to carry out recapitulating reviews of the current works on this issue in order to find the role of antidiabetic plants in resolution of health problems associated with this dysfunction.
    Rekha Nayaka MR*, Nayana Hashilkar, and Anupama
    At present, coronavirus disease 2019 (COVID-19), infected by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). It is feared that these viruses adapt to replication in humans and become transmissible from human to human. In addition, mutation in SARS-CoV-2 continue to cause outbreaks and cause an ever-increasing number of human cases with high fatality rates. The ongoing spread of this virus could potentially bring major challenges to worldwide health systems and consequences on the global economy and financial market if not controlled effectively. The development of effective drugs and vaccines against potentially pandemic viruses is therefore considered a priority. In this review, we discussed animal models that are used for the preclinical evaluation of drugs and novel candidate SARS-CoV-2 vaccines for the treatment and prevention of COVID 19 respectively. In most cases, a tier of multiple animal models is used before the evaluation of drugs and vaccine candidates in clinical trials is considered. Commonly, drugs and vaccines are tested for safety and efficacy in mice, ferrets, hamster and/or macaques. The use of each of these species has its advantages and limitations, which are addressed here.
    Gian Maria Pacifici*
    Lansoprazole is a proton pump inhibitor and is a prodrug. After absorption into the systemic circulation, the prodrug diffuses into the parietal cells of the stomach and accumulates in the acidic secretory canaliculi. Here, it is activated by proton-catalysed formation of a tetracyclic sulfenamide trapping the drug so that it cannot diffuse back across the canalicular membrane. The activated form then binds covalently with sulfhydryl groups of cysteine in the H+, K+-ATPase irreversibly inactivating the pump molecule. Acid secretion resumes only after new pump molecules are synthesized and inserted into the luminal membrane, providing a prodrug (up to 24 to 48 hours) suppression of acid secretion, despite the much shorter plasma elimination half-life of about 0.5 to 3 hours of the parent compound. Lansoprazole is used to promote healing of gastric and duodenal ulcers, and to treat gastroesophageal reflux disease, including erosive esophagitis. In newborns, the oral lansoprazole is 0.2 to 0.3 mg/kg once-daily, and in children, lansoprazole dose varies with the child body-weight. Lansoprazole has been found efficacy and safe in infants and children. Lansoprazole is converted into hydroxy lansoprazole by CYP2C19 and into lansoprazole sulfone by CYP3A4. The elimination half-life is less than 1 hour in infants and children. The treatment of infants and children with lansoprazole has been extensively studied and lansoprazole interacts with drugs. The aim of this study is to review lansoprazole dosing, efficacy and safety, pharmacokinetics, and the treatment in infants and children, and lansoprazole metabolism and interaction with drugs.
    Research Article
    Sebastián Chapela, Christian Congost, Manuel Alonso, Hilda Burgos, and Carlos Stella*
    The development of resistance to antifungals is a relevant issue during the treatment of infections. Using S. cerevisiae cells, we studied the effect of dichloroacetate (DCA), on the growth of the microorganism in the presence of fluconazole (FCZ). The results obtained show that DCA (2.0 - 3.0 mg/ml), sensitizes yeast cells to growth inhibition by fluconazole.
    Results indicate that the external pH reduction produced by DCA decreases the electrochemical proton gradient necessary for the extrusion of toxic compounds to yeast metabolism. This effect favors a synergism strategy leading to lower drug doses and reducing drugs side effects.
    Research Article
    Delia Teresa Sponza* and Buca Izmir
    In this study, the toxicity of a pharmaceutical industry wastewater was investigated by using six different trophic levels (four bacteria, a yeast, a mold, an algae a crustacean and a fish). The bacteria were Escherichia coli, Bacillus cereus, Vibrio fischeri, and Methane Archae Bacteria. The algae was Chlorella sp, the yeast was Candida sp, the fungi was Aspergillus, the crustacean was Daphnia magna and the fish was Lepistes sp.. Furthermore biodegradability and bioaccumulation tests were performed with two parmaceutical pollutants. The toxicity of this wastewater originated from its high sulfamethoxazole and oxytetracycline concentrations. This wastewater was treated by a reverse osmosis membrane reactor. The effects of increasing pressure on the rejections and recoveries of sulfamethoxazole and oxytetracycline was studied. Furthermore ,the effects of pH and temperature variations on the permeate yield was studied.The reverse osmosis reactor stability was not affected by pH, temperature and pressure increase. The toxicity of pharmaceutical industry wastewater decreased completely in the permeate, the biodegradability of the wastewater increased and it’s bioaccumulative properties disappered.
    Christina Nicolaeva Vidinova*
    Anti – VEGF therapy is the leading treatment strategy for AMD. Although this treatment generally improves VA of the affected patients, its prolonged application can lead to serious complications.
    Purpose: The purpose of our study is to outline the possible long term complications of anti-VEGF treatment in AMD patients and to outline eventual ways to avoid some of them.
    Methods: In our prospective study 42 patients with wet AMD were enrolled. They all underwent a complete ophthalmological examination including VA, fundus photography, structural OCT (Revue, Optovue) and OCT-A (Angiophlex, Zeiss). All of the patients were treated with aflibercept (Eylea) - in the Treat and Extend regiment for a period of 2 years. The mean number of injections was 15 +- 2. All patients were evaluated for possible complications after the 2 year period.
    Results: The long term complications we encounter can be summarized in percentage % as follows:
    - Tachyphylaxis to the treatment drug- 20%
    - RPE Tear-10 %
    - Retinal fibrosis and scar formation-32-35%
    - Retinal atrophy 25%
    In 20 % of the patients a tachyphylaxis developed after the first year, which leads to lower effect of the drug on the course of treatment. Discontinuation of the treatment or change to another drug helped against that complication. In 10% of the cases RPE tear developed- usually in cases with RPE detachment, large in area and height. Retinal fibrois was the most serious complication. In our study it developed mainly in patients with lower VA at baseline, with macular hemorrhages or intraretinal cysts Retinal fibrosis developed usually after the 8 intravitreal injection. In 25% retinal atrophy developed
    Conclusion: Complications of anti- VEGF therapy are relatively rare but leading to devastating results. The stronger the action of the anti-VEGF drug the more frequent the complications, especially fibrosis. Early recognition of the risk factors such as low vision at the beginning.intraretinal cysts, macular hemorrhages and large area of CNV are a prerequisite for a successful prophylaxis of the possible complication.
    Luisetto M*, Naseer Almukthar, Tarro G, Nili B. Ahmadabadi, Edbey Khaled Edbey K, Farhan Ahmad Khan, Gamal A. Hamid, Fiazza C, Cabianca L, Ilnaf, Yesvi A. Rafa, Mashori Gulam Rasool, Gadama G Prince, and Oleg Yurevich Llatyshev
    Aim of this work is to verify the state of the art related the use of graphene and its derivates in some vaccine technology (m RNA) , to show the chemical properties of this kind of carriers ( or extractive agent ) and to list the evidence at today related peculiarity involved in some covid-19 vaccine .The researcher will produce their own opinion about this topic. Of great relevance to verify the manifacturing procedure of this innovative product (m-RNA vaccine), and the tecnology and material used in purification phases.
    Review Article
    Sagir A, Raduka J, Budiansky A, Soliman A, Visos N, and Maurtua MA*
    Sufentanil is the most potent opioid use today in clinical practice, yet there is scarcity in the literature addressing this novel drug. The purpose of this article is to review sufentanil’s pharmacologic characteristics, the historical reasons for its development, and its current and future clinical applications after a recently developed sublingual formulation.
    Sharma VJ* and Bhagat SA
    The Covid-19 lockdown has severely affected the Indian education system. Nearly 290 million students in India have been out of School since March 2020 and worldwide nearly 94% student population (UN Report 2020) got impacted due to school closure. Ensuring learning continuity the government of India introduced several online free learning modules for students.
    Educational Institutions conducted online teaching and examinations session amid Covid-19 pandemic. ASER [4], an annual survey body in India reported that 38.2% children did not had access to smart phones while 11% children got smart phones post lockdown to help their studies. Both ASER and IMF (73), report highlight inadequacy of smart phones and internet connectivity as major hindrance for online education in India.
    We conducted a survey amid Covid-19 to examine the impact of e-learning from students and teachers point of view. Survey questionnaire were designed to study the advantages, disadvantages, challenges, and opportunities of e-Learning. The Survey infers that online teaching provides opportunities to students to have educators and study materials of their choice, provides safe environment at home amid Covid-19 crisis.
    Survey also revealed that 73.2% students disagreed to e-Learning process, 61.4% students faced difficulties related to eye irritation, headache, network issues, lack of practical knowledge against theory syllabus. 62.3% students agreed that offline mode is more effective.
    Amid many loopholes and challenges of this e-learning technology, e-learning came as an antidote in these exigencies of shutdown.
    JSciMed Central Peer-reviewed Open Access Journals
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