Drug Of First Choice Research Articles

Comparison of penicillins (penicillin G and ampicillin) and cefazolin as a definitive therapy against penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia in Japan: a retrospective cohort study

ObjectivesCefazolin has been the first-choice drug to treat penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia, because oxacillin and nafcillin are not approved in Japan. Since February 2019, cefazolin supply is stagnant in Japan because of possible contamination issues. To look for cefazolin alternatives that can be used as a definitive therapy, we evaluated the usefulness of penicillins (penicillin G and ampicillin) against PSSA bacteremia. MethodsA retrospective cohort study of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia was conducted between January 2012 and September 2017. MSSA was determined according to the Clinical and Laboratory Standards Institute guidelines. PSSA was defined as S. aureus with penicillin G minimum inhibitory concentration of ≤0.03 mg/L without using the zone edge test or blaZ PCR. ResultsOf the 280 patients with MSSA bacteremia enrolled, and 138 (49.3%) was PSSA. Of the 44 patients who met the inclusion criteria, 11 were administered penicillins (penicillin G, n = 3 and ampicillin, n = 8) and 33 with cefazolin. Although the patients in the two groups had similar demographics, those in the penicillins group had significantly lower median Charlson score [interquartile range] than those in the cefazolin group (0[0–1] vs 1[0–4], p = 0.033). The two groups showed no significant differences regarding adverse events and bacteremia recurrence. None of the patients in the penicillins group died; however, 5 (15.2%) patients in the cefazolin group showed a 30-days mortality. ConclusionPenicillins can be useful as a definitive therapy against PSSA bacteremia with stable condition, and they can be an alternative to cefazolin.

Analysis of urinary metabolic alteration in type 2 diabetic rats treated with metformin using the metabolomics of quantitative spectral deconvolution 1H NMR spectroscopy

Metformin has been used clinically as the first-choice drug to treat type 2 diabetes patients. It is not metabolized in liver and the residue which is excreted unchanged in the urine. Identification and quantification of metformin in the urine can be used as a unique marker for the metformin treated diabetic patients. The aim of our study was to identify residual metformin in the urine of type 2 diabetic rats using quantitative spectral deconvolution of 1H NMR method. Additionally, quantitative assessment of residual metformin and other identified metabolites in the urine, as well as the evaluation of metabolic alteration due to metformin treatment of diabetic condition were also carried out. Partial least square discriminant analysis (PLS-DA) and statistical analysis were used to discriminate the metformin treated type 2 diabetic, the lean, the obese, and the type 2 diabetic rat groups. Furthermore, in order to evaluate the statistical difference of metabolite levels between the groups, ANOVA test was performed. The presence of metformin in the urine of the metformin treated diabetic rats from the 1H NMR spectral analysis and its identity was confirmed by 2D NMR spectroscopy experiments including the 2D 1H J-resolved (JRES), and 1H heteronuclear multiple correlation (HMBC). Based on the PLS-DA model and statistical analysis, it was established that metformin treatment significantly influenced the improvement of glucose and 1-methylnicotinamide metabolism; increase the growth and activity of gut microbiota as indicated by the elevation of trimethylamine (TMA), phenylacetylglycine (PAG) and indoxylsulfate levels; as well as the suppression of tricarboxylic acid (TCA) cycle metabolism as shown by the decreased levels of citrate, 2-oxoglutarate, succinate, and fumarate. This study provided new approach to the quantitative analysis of metformin in urine and further exploration on the effect of metformin treatment on the type 2 diabetic rats revealed useful findings on its metabolic states.

Chronic lower back pain: diagnosis and current principles of therapy

Chronic nonspecific lower back pain (LBP) is one of the most common causes of adult disability. The chronic course of back pain is often supported by the patient's unhealthy lifestyle and the use of ineffective treatments. The combination of cognitive behavioral therapy, therapeutic exercises, gradually increased physical activity, and rational pharmacotherapy are effective in most cases of chronic non-specific LBP. In this disease, nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-choice drugs that should be prescribed in a short cycle. The choice of NSAIDs is determined by the presence of concurrent diseases in the patient and by the risk of developing adverse events. The paper discusses the efficacy and safety of meloxicam in non-specific NSAIDs.

Topical treatment of oral lichen planus

Oral lichen planus (OLP) is a skin disease affecting the mouth, which can cause a burning or stinging discomfort in the mouth when eating or drinking. Ulcers may occur and these are especially painful. The cause of oral lichen planus is not known in most instances, but it is likely to be related to the body's immune system. In this study, the authors from China aimed to compare the efficacy and safety of drugs called topical calcineurin inhibitors (TCI) with medicines applied to the skin called topical corticosteroids (TCS), in the treatment of OLP. The authors looked at globally published randomized controlled trials (RCTs) reporting TCI (tacrolimus, pimecrolimus, and cyclosporine) compared with TCS for OLP from eight medical databases. Twenty‐one RCTs with a total of 965 patients published between 1995 and 2017 were included (tacrolimus‐TCS: 12 studies, 578 patients; pimecrolimus‐TCS: 3 studies, 98 patients; cyclosporine‐TCS: 6 studies, 289 patients). The authors found that TCI including tacrolimus, pimecrolimus and cyclosporine were similar to TCS in efficacy for the short‐term treatment of OLP (3‐8 weeks). In addition, tacrolimus 0.1% was similar to TCS in relapse rate. The blood levels of tacrolimus and cyclosporine were usually extremely low, while the few cases of patients with high levels may have been caused by swallowing the drug accidentally. Although a few adverse events (unwanted side effects) were observed in the tacrolimus and cyclosporine groups, no serious events were found. Therefore, TCI may be an alternative approach when OLP does not improve with use of TCS. Due to the limited trials of pimecrolimus and cyclosporine, as well as a few adverse events and high cost of cyclosporine, tacrolimus 0.1% should be the first drug of choice in TCI for the short‐term treatment of OLP that is not improving with TCS. More well‐designed RCTs are needed to evaluate the long‐term efficacy and safety of TCI compared with TCS.

Consensus of the Hellenic Headache Society on the diagnosis and treatment of migraine

More than 0.6 million people suffer from disabling migraines in Greece causing a dramatic work loss, but only a small proportion of migraineurs attend headache centres, most of them being treated by non-experts. On behalf of the Hellenic Headache Society, we report here a consensus on the diagnosis and treatment of adult migraine that is based on the recent guidelines of the European Headache Federation, on the principles of Good Clinical Practice and on the Greek regulatory affairs. The purposes are three-fold: (1) to increase awareness for migraine in Greece; (2) to support Greek practitioners who are treating migraineurs; and (3) to help Greek migraineurs to get the most appropriate treatment. For mild migraine, symptomatic treatment with high dose simple analgesics is suggested, while for moderate to severe migraines triptans or non-steroidal anti-inflammatory drugs, or both, should be administered following an individually tailored therapeutic strategy. A rescue acute treatment option should always be advised. For episodic migraine prevention, metoprolol (50–200 mg/d), propranolol (40–240 mg/d), flunarizine (5–10 mg/d), valproate (500–1800 mg/d), topiramate (25–100 mg/d) and candesartan (16–32 mg/d) are the drugs of first choice. For chronic migraine prevention topiramate (100-200 mg/d), valproate (500–1800 mg/d), flunarizine (5–10 mg/d) and venlafaxine (150 mg/d) may be used, but the evidence is very limited. Botulinum toxin type A and monoclonal antibodies targeting the CGRP pathway (anti-CGRP mAbs) are recommended for patients suffering from chronic migraine (with or without medication overuse) who failed or did not tolerate two previous treatments. Anti-CGRP mAbs are also suggested for patients suffering from high frequency episodic migraine (≥8 migraine days per month and less than 14) who failed or did not tolerate two previous treatments.

Therapeutic Approaches for Peripheral and Central Neuropathic Pain.

Neuropathic pain is a chronic secondary pain condition, which is a consequence of peripheral or central nervous (somatosensory) system lesions or diseases. It is a devastating condition, which affects around 7% of the general population. Numerous etiological factors contribute to the development of chronic neuropathic pain. It can originate from the peripheral part of the nervous system such as in the case of trigeminal or postherpetic neuralgia, peripheral nerve injury, painful polyneuropathies, or radiculopathies. Central chronic neuropathic pain can develop as a result of spinal cord or brain injury, stroke, or multiple sclerosis. As first-line pharmacological treatment options, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids are recommended. In trigeminal neuralgia, carbamazepine and oxcarbazepine are the first-choice drugs. In drug-refractory cases, interventional, physical, and psychological therapies are available. This review was structured based on a PubMed search of papers published in the field from 2010 until May 2019.

The CoDiNOS trial protocol: an international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia

IntroductionCongenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity...

The Efficacy and Evidence-Based Use of Biologics in Children and Adolescents: Using Monoclonal Antibodies and Fusion Proteins as Treatments.

Monoclonal antibodies (mAb) and fusion proteins (FP) are increasingly being used in children and adolescents. In this review, we analyze the evidence for their safety and efficacy in the treatment of the most common chronic inflammatory diseases. We systematically searched PubMed, AWMF.org, and other databases for high-quality trials (i.e., randomized controlled trials with clinical primary endpoints) and guidelines published at any time up to 10 December 2018 that dealt with mAb and FP that are approved for pediatric use. The search term was "monoclonal anti- body/fusion protein [e. g. adalimumab] AND children." The 620 hits included 25 high-quality trials (20 of them manufacturer- sponsored) on 9 mAb/FP (omalizumab, adalimumab, etanercept, ustekinumab, infliximab, golimumab, anakinra, canakinumab, tocilizumab, and abatacept), as well as 6 guidelines (3 each of levels S3 and S2k) on the treatment of bronchial asthma, psoriasis, juvenile idopathic arthritis, and chronic inflammatory bowel diseases. For none of these conditions are mAb and FP the drugs of first choice. Adverse drug effects are rare but sometimes severe (infection, immune dysregulation, tumors). The retrieved trials have deficiencies that make it difficult to reliably evaluate the efficacy, safety, and utility of mAb/FP for children and adolescents with chronic inflammatory diseases. mAb/FP nonetheless represent a treatment option to be considered in case conventional immune-modulating drugs are ineffective. Researcher-initiated, high-quality trials and manufacturer-independent, systematic long-term evaluations of adverse effects (e.g., tumors) are sorely needed.

Clinical experiences with the use of oxytocin injection by healthcare providers in a southwestern state of Nigeria: Across-sectional study.

BackgroundPostpartum hemorrhage (PPH) is a leading cause of maternal mortality in Nigeria and in most low- and middle-income countries. The World Health Organization (WHO) strongly recommends oxytocin as effective, affordable, and the safest drug of first choice in the prevention and treatment of PPH in the third stage of labor. However, there are concerns about its quality. Very high prevalence of poor-quality oxytocin, especially in Africa and Asia, has been reported in literature. Excessive and inappropriate use of oxytocin is also common in low-resource settings.ObjectiveTo assess clinical experiences with quality of oxytocin used by healthcare providers in Lagos State, Nigeria.MethodsThis was a descriptive cross-sectional study conducted in 2017, with 705 respondents (doctors and nurses) who use oxytocin for obstetrics and gynecological services recruited from 195 health facilities (public and registered private) across Lagos State. Data collection was quantitative, using a pretested self-administered questionnaire. Data analysis was performed with IBM SPSS version 21. Statistical significance was set at 5 percent (p<0.05). Ethical approval was obtained from Lagos University Teaching Hospital Health Research Ethics Committee.ResultsOnly 52 percent of the respondents knew oxytocin should be stored at 2°C to 8°C. About 80 percent of respondents used oxytocin for augmentation of labor, 68 percent for induction of labor, 51 percent for stimulation of labor, and 78 percent for management of PPH. Forty-one percent used 20IU and as much as 10% used 30IU to 60IU for management of PPH. About 13 percent of respondents reported believing they had used an ineffective brand of oxytocin in their practice. Just over a third (36%) had an available means of documenting or reporting perceived ineffectiveness of drugs in their facility; of these, only about 12 percent had pharmacovigilance forms in their facilities to report the ineffectiveness.ConclusionThe inappropriate and inconsistent use of oxytocin, especially overdosing, likely led to the high perception of medicine effectiveness among respondents. This is coupled with lack of suspicion of medicine ineffectiveness by clinicians as a possible root cause of poor treatment response or disease progression. Poor knowledge of oxytocin storage and consequent poor storage practices could have contributed to the ineffectiveness reported by some respondents. It is necessary to establish a unified protocol for oxytocin use that is strictly complied with. Continuous training of healthcare providers in medicine safety monitoring is advocated.

Prophylactic antibiotic usage by Belgian veterinarians during elective caesarean section in Belgian blue cattle

The use of prophylactic antibiotics in veterinary surgery reduces the occurrence of postoperative complications. In order to limit the development of antimicrobial resistance in bacteria and to maximize therapy efficacy, antibiotics should be used prudently and efficiently. A survey was sent to Wallonian rural veterinarians in order to assess the use of antibiotics before, during and after bovine elective caesarean section, the most common surgical procedure in Belgian rural practice. Results were analysed in the light of the current guidelines formulated by the Belgian Centre of Expertise on Antimicrobial Consumption and Resistance in Animals.Among 380 contacted veterinarians, 113 answered the survey. All veterinarians use antibiotics during caesarean section. Veterinarians predominantly use penicillin as the first drug of choice, whereas a minority use drugs considered as second or third choice, such as amoxicillin, oxytetracyclin or lincomycin-spectinomycin. Also, 31/113 veterinarians simultaneously use molecules from different antibiotic classes. The majority (100/113) of veterinarians inject antibiotics during or after surgery, while a minority (13/113) administer antibiotics preoperatively. Most veterinarians (67/113) limit the duration of their antibiotic treatment to 1 day. Considering the administration route, most veterinarians (88/113) systematically use the intraperitoneal injection route, which is not registered. Intramuscular injection and injection between muscle layers during surgery are carried out by 82/113 and 43/113 respondents, respectively. Twenty-two respondents apply intra-uterine antibiotics. Most veterinarians (87/113) combine several administration routes. The dosage of antibiotics varies enormously and excessive injection volumes are common, especially when multiple injection routes are combined.Our results show a striking lack of consistency in the antibiotic therapy during elective CS by rural veterinarians. Whereas the drug of choice and the treatment duration were largely in line with the current guidelines, this is certainly not the case for the dosage and the administration route. The intraperitoneal injection of antibiotics cannot be justified. Incorrect dosage of antibiotics should be avoided at all cost. The use of second and third line molecules and the simultaneous use of different antibiotic classes should be discouraged. A major challenge lies in the education of veterinary students and the sensitization of practitioners to avoid or unlearn unnecessary habits concerning antibiotic use. Finally, more clinical trials are needed in order to refine the current guidelines for antibiotic use and to determine the optimal drug of choice, treatment moment and application route in elective caesarean section in cattle.

Antifungal screening and in silico mechanistic studies of an in-house azole library.

Systemic Candida infections pose a serious public health problem with high morbidity and mortality. C.albicans is the major pathogen identified in candidiasis; however, non-albicans Candida spp. with antifungal resistance are now more prevalent. Azoles are first-choice antifungal drugs for candidiasis; however, they are ineffective for certain infections caused by the resistant strains. Azoles block ergosterol synthesis by inhibiting fungal CYP51, which leads to disruption of fungal membrane permeability. In this study, we screened for antifungal activity of an in-house azole library of 65 compounds to identify hit matter followed by a molecular modeling study for their CYP51 inhibition mechanism. Antifungal susceptibility tests against standard Candida spp. including C.albicans revealed derivatives 12 and 13 as highly active. Furthermore, they showed potent antibiofilm activity as well as neglectable cytotoxicity in a mouse fibroblast assay. According to molecular docking studies, 12 and 13 have the necessary binding characteristics for effective inhibition of CYP51. Finally, molecular dynamics simulations of the C.albicans CYP51 (CACYP51) homology model's catalytic site complexed with 13 were stable demonstrating excellent binding.

Mouth Dissolving Tablets-Pediatric and Geriatric Patient Compliance Dosage Forms

The oral route of administration remains the most convenient route of administration but the major disadvantage is dysphagia (difficulty in swallowing) to overcome these problems novel drug delivery systems have developed mouth dissolving tablets with improved patient compliance. Mouth dissolving tablets are solid dosage forms which dissolve rapidly when kept in mouth. The first choice of drugs for pediatric, geriatric, mentally disable patients and also for patients who are traveling can administer the tablet any time without the need for water. conventional technologies and patented technologies are the two different technologies used in the manufacturing of MDTs. This review describes the various aspects of MDT formulation, super disintegrants, and technologies used for developing MDT, along with evaluation.

Is the approach of delirium in Dutch nursing-homes in accordance with the national guideline?

Delirium is a common disorder, affecting many patients in nursing-homes, with large impact on patients. Implementation of good care and treatment can potentially prevent development of a delirium or may reduce the severity or duration. This research was conducted to get an impression of delirium care in Dutch nursing homes, and of the implementation of the recommendations of the national guideline. 1. How many Dutch nursing homes have a local protocol for delirium?2. To what extend do doctors, specialised in care for older people in nursing homes, screen, diagnose and treat delirium according to the Dutch guideline for delirium? Between June and December 2016, Dutch nursing homes were approached with an online questionnaire. Data were collected in Survey Monkey and descriptive analyses were performed. 68 nursing homes were included. 32% of the nursing homes had a local delirium protocol. 48% of the doctors knew about the national guideline delirium, 60% used preventive measures, and screening instruments were used in 98%. 29% used diagnostic criteria. Non-medical interventions were applied by 96%. In 98%, haloperidol was the drug of first choice. Preventive antipsychotics were prescribed by 21%. Only a third of the organisations developed a local delirium protocol. Standardising delirium care by a local delirium protocol, with special attention for prevention, diagnostics and aftercare of delirium, can be an important step in improving the quality of care in nursing homes.

Short- and long-term safety of oral propranolol in the treatment of infantile hemangioma

Infantile hemangioma is the most common tumor in infancy, with an incidence of 4% - 5%. According to the risk level, hemangioma is divided into 3 levels: high risk, medium risk and low risk. At present, the first-line treatment of high-risk hemangioma is oral propranolol (β-receptor blockers) . It has been 10 years since infantile hemangioma was treated with propranolol for the first time, and propranolol has been the drug of first-choice in systematic treatment due to its high efficacy and good safety, but its long-term adverse effect needs further evaluation. Key words: Hemangioma; Propranolol; Infant; Long-term safety; Short-term safety

Efficacy of manganese oxide (Mn2O3) nanoparticles against Leishmania major in vitro and in vivo

BackgroundThe pentavalent antimonial compounds are the first drug of choice for leishmania infection, but have several side effects that cause some restriction for use. Extension of nanoparticle use in biological research and proven effectiveness of manganese nanoparticles on fungi and bacteria, along with the lack of information about its antileishmanial effects, have motivated this study. Manganese can induce cell apoptosis by increasing FOXO3a-Bim/PUMA mRNA activation and activating of caspase-3 pathway. MethodsThis study was aimed to examine the efficacy of manganese oxide nanoparticles againstLeishmania major (MRHO/IR/75/ER) in vitro and in vivo. To evaluate the antileishmanial activity of NPs, light microscopic observation was used to determine the number of remaining parasites in each well. The MTT test was used to determine the cytotoxicity effects of Mn2O3 NPs against L. major promastigotes and macrophage cells. The effect of nanoparticles on cultured amastigotes under in vitro conditions was also investigated. The possible apoptosis of L. major by Mn2O3 NPs was evaluated with flow cytometry assay. Additionally, the preventive and therapeutic effects of Mn2O3 NPs in BALB/c mice following cutaneous L. major infection was tested. The effect of Mn2O3 NPs on promastigotes and amastigotes were proven by MTT assay and amastigote assay, respectively. ResultsThe IC50 value of Mn2O3 NPs against L. major promastigotes and macrophages was 15 and 40 μg ml−1 respectively. The results of flow cytometry showed about 57% of the promastigotes were induced to apoptosis with Mn2O3 NPs. In in vivo studies, the size of the ulcers were significantly reduced, and the survival rate of the mice, in comparison with the control group, was increased. ConclusionMn2O3 NPs has a beneficial effect on L. major promastigotes in vitro and in vivo and could be considered as a candidate for the treatment of this infection.

Management of epilepsy in brain tumors.

Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients' representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September-October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care.

Disability and Therapeutic Response in Paediatric Neuromyelitis Optica Spectrum Disorder: A Case Series from Iran.

The characteristics ofpaediatric neuromyelitis optica spectrum disorder (NMOSD) may indicate the degree of disability and identify factors that predict the response to treatment. Among 114 NMOSD patients in an acquired demyelinating syndromes registry at the Sina Hospital, in Tehran, Iran, 10 paediatric NMOSD patients with longitudinal follow-up from 2005 to 2016 were retrospectively identified. The median time between disease onset and diagnosis was 18 months (range 1-108 months). All patients had a relapsing course, which resulted in disability in six with severe visual impairment and functional blindness in one and impaired ambulation in five patients during follow-up. Azathioprine (AZA) was first drug of choice for prophylaxis, but in five patients new attacks occurred and therapy was switched to rituximab (RTX) with no further relapses after median two years (range 1-3 y) follow-up. Paediatric onset of NMOSD was associated with severe attacks and poor response in 50 % of cases to AZA, RTX seemed to decrease the relapse rate.

Topical calcineurin inhibitors in the treatment of oral lichen planus: a systematic review and meta-analysis.

TCS (topical corticosteroids) are the first-line drug in the treatment of oral lichen planus (OLP). However, the value of topical calcineurin inhibitors (TCI) including tacrolimus, pimecrolimus and ciclosporin for OLP is still controversial. To compare the efficacy and safety of TCI vs. TCS for OLP. The authors searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and four Chinese databases from 1950 to May 2018. The randomized controlled trials comparing TCI and TCS for OLP reported at least one of the following outcomes: improvement of clinical signs and/or symptoms, relapse, blood levels of TCI and adverse events. Twenty-one trials involving 965 patients were included in the analysis. For the treatment of OLP (3-8 weeks), TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy. Tacrolimus-TCS resulted in similar outcomes, with relapse at 3 weeks to 6 months. Blood levels of TCI were usually undetectable. In addition, tacrolimus showed a statistically higher incidence of local adverse events than TCS for short-term treatment. A few systemic adverse events occurred in the tacrolimus and ciclosporin groups, but they were not serious. The evidence for tacrolimus (n = 12), pimecrolimus (n = 3) and ciclosporin (n = 6) demonstrated that treatment with TCI may be an alternative approach when OLP does not respond to the standard protocols. Tacrolimus 0·1% should be the first drug of choice when selecting TCI for short-term treatment in recalcitrant OLP. Further well-designed trials are warranted to evaluate the long-term efficacy and safety of TCI. What's already known about this topic? The main topical drug for oral lichen planus (OLP) is topical corticosteroids (TCS). Patients with OLP who are not responsive to TCS or are at risk of adverse events from TCS need other alternative drugs. Topical calcineurin inhibitors (TCI), including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune-mediated diseases. What does this study add? TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy for the short-term treatment of OLP. The local adverse events of tacrolimus were higher than with TCS. A few systemic adverse events were reported with TCI, but they were all tolerable and not serious. The limited evidence for pimecrolimus (three trials) and ciclosporin (six trials) requires further studies to evaluate the short-term and long-term efficacy and safety of TCI compared with TCS.

Correlation study of antibacterial activity and spectrum of Penicillins through a structure-activity relationship analysis

Penicillins are a group of antibiotics of the beta-lactam group, widely used worldwide as first-choice drugs in the treatment of infections caused by sensitive bacteria. Their use is based on an empirical measure of their activity through antibiograms. In this work we have carried out a structure-activity relationship analysis to elucidate the molecular and physicochemical bases that determine the antibacterial activity and the orientation of the antibacterial spectrum of penicillins, employing a set of bacteria that cause common infections. It was found that the antibacterial activity increases as penicillin size increases for both, Gram-negative and Gram-positive bacteria. In the same way, liposolubility affects the activity; water soluble penicillins have greater activity on Gram-negative bacteria, while in some cases liposoluble penicillins present higher activity against Gram-positive bacteria. In addition, it is proposed that electronic properties of the substituent of the penicillin core determine its antibacterial spectrum. The electron donating substituents make the penicillin active against Gram-positive bacteria, while the electron withdrawing substituents gear the activity towards Gram-negative bacteria. In addition, the alpha-carbon (Cα) of the carboxamide side chain is also essential for the activity against Gram-negative bacteria; penicillins that lack it, have higher activity against Gram-positive bacteria.

Kidney protective effect of acalypha indica linn. root extract in high-fructose and high-cholesterol diet-fed rats

Diet high in fructose and cholesterol may lead to the development of diabetic nephropathy (DN). One of the first drugs of choice in DN treatment is captopril. Prolonged use of this drug may lead to some adverse effects and the treatment can be optimized through using other therapy options. Acalypha indica Linn. (AI) may be an alternative herbal therapy for DN. The objective of this research is to investigate the renoprotective effect of AI on DN. For seven weeks, thirty-two Sprague-Dawley rats were divided into groups receiving normal diet and high-fructose and high-cholesterol diet (HFCD). Then, the HFCD-fed rats were divided into four groups receiving different treatment: negative control, AI root extract (250 mg/kgBW), captopril (2.5 mg/kgBW), and combination of captopril and AI. Normal diet group was divided into AI and no treatment. After four weeks of treatment, the rats were terminated and serum urea and creatinine levels were measured. In the normal group, AI therapy decreased serum urea and creatinine levels. In the HFCD groups, AI and captopril monotherapy groups had increased serum urea levels, but lower compared to negative control. Meanwhile, serum creatinine levels decreased in both groups. However, these findings are not statistically significant. We found that combination therapy group had the highest increase in serum urea level, which was significantly different with captopril group (p=0.01). Serum creatinine level was also increased in this group. Our present study showed that AI tend to reduce serum urea and creatinine levels in normal diet group and inhibit the increase of serum urea and creatinine levels in rats fed with HFCD diet. Antagonistic interaction between captopril and AI might be present.