Monotherapeutic Treatment Research Articles

Sleep and behavioral disturbances induced by epilepsy: Protective effect of Gabapentin

Numerous sleep disturbances induced by nocturnal epilepsy have been reported. Gabapentin (GBP) is used as an adjuvant or as a monotherapeutic treatment as it induces significant improvement in patients with partial or secondaryly widespread focal seizures. In experimental animal models of epilepsy with pentilenetetrazole (PTZ), GBP protects against the generated seizures. The objective of this work was to investigate its effectiveness in protecting against motor and sleep disturbances caused by seizures. Polygraphic studies were conducted in male wistar rats, separated into 4 groups. After administration of saline solution, a check record was carried out on each group. Subsequently, one group received 50 mg/kg of PTZ, while the other three groups received 15, 30 or 60 mg/kg GBP, 30 minutes prior to PTZ administration. After administration of PTZ, electrophysiological and behavioral manifestations characterizing seizures were observed. In addition, surveillance states were significantly altered, increasing the amount of wakefulness, while sleep was inhibited over a period of time. The administration of increasing doses of GBP tended to inhibit the presence of abnormal motor behaviors, facilitating the presence of sleep.

Schistosome TRPML channels play a role in neuromuscular activity and tegumental integrity

Schistosomiasis is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma. Mono-therapeutic treatment of this disease with the drug praziquantel, presents challenges such as inactivity against immature worms and inability to prevent reinfection. Importantly, ion channels are important targets for many current anthelmintics. Transient receptor potential (TRP) channels are important mediators of sensory signals with marked effects on cellular functions and signaling pathways. TRPML channels are a class of Ca2+-permeable TRP channels expressed on endolysosomal membranes. They regulate lysosomal function and trafficking, among other functions. Schistosoma mansoni is predicted to have a single TRPML gene (SmTRPML) with two splice variants differing by 12 amino acids. This study focuses on exploring the physiological properties of SmTRPML channels to better understand their role in schistosomes. In mammalian cells expressing SmTRPML, TRPML activators elicit a rise in intracellular Ca2+. In these cells, SmTRPML localizes both to lysosomes and the plasma membrane. These same TRPML activators elicit an increase in adult worm motility that is dependent on SmTRPML expression, indicating a role for these channels in parasite neuromuscular activity. Suppression of SmTRPML in adult worms, or exposure of adult worms to TRPML inhibitors, results in tegumental vacuolations, balloon-like surface exudates, and membrane blebbing, similar to that found following TRPML loss in other organisms. Together, these findings indicate that SmTRPML may regulate the function of the schistosome endolysosomal system. Further, the role of SmTRPML in neuromuscular activity and in parasite tegumental integrity establishes this channel as a candidate anti-schistosome drug target.

High-Dose-Rate Brachytherapy as Monotherapy for Low- and Intermediate-Risk Prostate Cancer. Oncological Outcomes After a Median 15-Year Follow-Up.

IntroductionTo evaluate the oncological outcome of high dose rate (HDR) brachytherapy (BRT) as monotherapy for clinically localised prostate cancer (PCA).Material and MethodsBetween January 2002 and February 2004, 141 consecutive patients with clinically localised PCA were treated with HDR-BRT monotherapy. The cohort comprised 103 (73%) low-, 32 (22.7%) intermediate- and 6 (4.3%) high risk patients according to D’Amico classification or 104 (73.8%) low-, 24 (17.0%) intermediate favourable-, 12 (8.5%) intermediate unfavourable- and one (0.7%) very high risk patient according to National Comprehensive Cancer Network (NCCN) one. Patients received four fractions of 9.5 Gy delivered within a single implant up to a total physical dose of 38 Gy. Catheter-implantation was transrectal ultrasound-based whereas treatment planning CT-based. Thirty-three patients (23.4%) received ADT neoadjuvantly and continued concurrently with BRT. Biochemical relapse-free survival (BRFS) was defined according to the Phoenix Consensus Criteria and genitourinary (GU)/gastrointestinal (GI) toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 5.0.ResultsMedian age at treatment and median follow-up time was 67.2 and 15.2 years, respectively. Twenty-three (16.3%) patients experienced a biochemical relapse and 5 (3.5%) developed distant metastases, with only one patient dying of PCA. The BRFS was 85.1% at 15 years and 78.7% at 18 years. The corresponding overall survival, metastases-free survival, and prostate cancer specific mortality at 15- and 18-years was 73.9%/59.1%, 98.3%/90.6%, and 100%/98.5% respectively. Late grade 3 GI and GU toxicity was 4.2% and 5.6% respectively. Erectile dysfunction grade 3 was reported by 27 (19%) patients. From the prognostic factors evaluated, tumor stage (≤T2b compared to ≥T2c) along with the risk group (low-intermediate vs. high) when using the D’Amico classification but not when the NCCN one was taken into account, correlated significantly with BRFS.ConclusionOur long-term results confirm HDR-BRT to be a safe and effective monotherapeutic treatment modality for low- and intermediate risk PCA.

A Review on Deadly Nipah Virus - Prevalence and its Management

NiV is an emerging infectious disease caused by infected bats from the family of Paramyxoviridae. From its secretions the disease can be spread to humans or through close contact with infected humans. NiV was detected for the first time in 1998 in Malaysia. NiV have broad species tropism and potential that may evolve life threatening respiratory and/ or neurologic disease in humans and as well as in animals which make them important trans-boundary biological threats. The disease presented mainly as acute encephalitis with a short incubation period of less than two weeks (4 to 18 days), with the main symptoms of fever, headache and giddiness followed by coma. The major involvement of the lung and brain in NiV infection often manifested as an acute severe respiratory syndrome, encephalitis etc. In case of Henipavirus the diagnosis of infection is mainly based on the details of contact with diseased animals, evidence of encephalitis and or pneumonia, with serologic evidence of infection using Enzyme Linked Immunosorbant (EIA) assay testing or polymerase chain reaction. The anti-viral drug Ribavirin is a well-known first line treatment strategy for suspected viral infections of unknown etiology. Based on a study conducted to discover whether combining monotherapeutic treatments with Ribavirin and Chloroquine would result in any protection indicative of favourable drug-drug interactions when treatment were initiated with lethal inoculums of NiV. The reason for multiple outbreaks may be due to low healthcare system capacity and robust surveillance strategy contributes to it. Multidisciplinary and multiple facet approach is vital in preventing the emergence of NiV. It is crucial to undertake rigorous research for developing vaccines and medicines to prevent and treat NiV.

Effect of oligoribonucleotides with D-mannitol complexes on oxidative stress indicators against thioacetamide-induced liver fibrosis

The aim of the study. To determine the effect of oligoribonucleotides-D-mannitol complexes (ORN-D-M) on the indicators of oxidative destruction of biomolecules and the antioxidant system of cells in thioacetamide (TAA)-induced liver fibrosis.Materials and methods. Liver fibrosis was induced for 8 weeks by intraperitoneal administration of TAA (150 mg/kg body weight). ORN-D-M (200 mg/kg per os) was administered orally during intoxication. At the end of the experiment, the liver was excised and examined for the content of oxidative stress products and the activity of antioxidant enzymes. Data were analyzed using the ANOVA test followed by Tukey post hoc testing.Results. It is shown that the monotherapeutic treatment of ORN-D-M in TAA-induced liver fibrosis has a pronounced protective effect, which is manifested in the reduction of oxidative stress. ORN-D-M led to the attenuation of free radical damage of biopolymers, which was manifested in a decrease in the levels of peroxidation products of lipids and proteins with a simultaneous increase in the level of protein thiol groups and reduced glutathione. In addition, treatment with complexes increased the activity of the antioxidant defence system of cells.Conclusions. The obtained results indicate that ORN-D-M complexes have a potential hepatoprotective effect in TAA-induced liver fibrosis. The complexes are able to effectively reduce the indicators of oxidative damage of biomolecules with a simultaneous increase in the activity of enzymes of the antioxidant system in TAA-induced fibrosis

Permissive Fatty Acid Incorporation Promotes Staphylococcal Adaptation to FASII Antibiotics in Host Environments

The essentiality of fatty acid synthesis (FASII) products in the human pathogen Staphylococcus aureus is the underlying rationale for FASII-targeted antimicrobial drug design. Reports of anti-FASII efficacy in animals support this choice. However, restricted test conditions used previously led us to investigate this postulate in a broader, host-relevant context. Wereport that S.aureus rapidly adapts to FASII antibiotics without FASII mutations when exposed to host environments. FASII antibiotic administration upon signs of infection, rather than just after inoculation as commonly practiced, fails to eliminate S.aureus in a septicemia model. Invitro, serum lowers S.aureus membrane stress, leading to a greater retention of the substrates required for environmental fatty acid (eFA) utilization: eFAs and the acyl carrier protein. In this condition, eFA occupies both phospholipid positions, regardless of anti-FASII selection. Our results identify S.aureus membrane plasticity in host environments as a main limitation for using FASII antibiotics in monotherapeutic treatments.

Role of janus kinase inhibitors in the treatment of rheumatic diseases

Janus kinases inhibitors (JAKI) are new orally administrable disease-modifying antirheumatic drugs (DMARD) for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), representing a treatment alternative equally effective as biological DMARD that is also classified equivalent in the guidelines. JAKI reversibly inhibit intracellular signal transduction from the cytokine receptor to the nucleus. Tofacitinib and baricitinib, two JAKI already approved for RA treatment, are taken once or twice a day, respectively, and two more are expected to receive approval next year. Tofacitinib is also approved for PsA. Generally, JAKI are initially used in combination with methotrexate (MTX) but are equally effective as monotherapeutic treatment if MTX is contraindicated. In terms of therapy safety, JAKI and bDMARD are generally comparable with one exception: JAKI are associated with an increased risk of herpes zoster infection. JAKI treatment requires laboratory blood tests, especially blood count, transaminases and creatinine. Due to hepatic metabolization, tofacitinib is associated with certain drug interactions. Altogether JAKI enhance treatment possibilities for diseases such as RA and PsA combining the same effectiveness and safety as bDMARD with the option of oral administration.

Combating breast cancer using combination therapy with 3 phytochemicals: Piperine, sulforaphane, and thymoquinone.

Despite the significant advances in screening methods for early diagnosis, breast cancer remains a global threat and continues to be the leading cancer diagnosed in women, requiring effective therapy. Currently, combination therapy has become the hallmark of breast cancer treatment due to the high incidence of tumor recurrence and disease progression after monotherapeutic treatments, including surgery, radiotherapy, endocrine therapy, and chemotherapy. Over the past decades, there has been considerable interest in studying the anticancer effect of bioactive phytochemicals from medicinal plants combined with these conventional therapies. The rationale for this type of therapy is to use combinations of drugs that work by different mechanisms, thereby decreasing the likelihood that cancer cells will develop resistance, and also reduce the therapeutic dose and toxicity of single treatments. Three agents have received great attention with regard to their anticancer properties: 1) piperine, a dietary phytochemical isolated from black pepper (Piper nigrum L.) and long pepper (Piper longum L.); 2) sulforaphane, an isothiocyanate mainly derived from cruciferous vegetables; and 3) thymoquinone, the active compound from black seed (Nigella sativa L.). This review focused on the combined effect of these 3 compounds on conventional cancer therapy with the objective of observing enhanced efficacy compared with single treatments. This review also highlights the importance of the nanoformulation of such bioactive phytochemicals that could enhance their bioavailability by providing an efficient targeted delivery system with a reduced systemic dose while resulting in a more efficient dosing at the target site.

Effect of gabapentin on sleep patterns disturbed by epilepsy

For a long time, numerous sleep alterations induced by nocturnal epilepsy have been described. Such alterations include sleep fragmentation, decrement of sleep efficiency, increment of the wake time after sleep onset (WASO), increment of light sleep, and decrement of sleep depth. On the other hand, gabapentin (GBP), an antiepileptic drug analog of γ-aminobutyric acid (GABA) used as adjunctive and eventually, as a monotherapeutic treatment, induces a significant improvement in patients with both focal and secondarily generalized partial seizures. In experimental epilepsy models, this drug protects against pentylenetetrazol (PTZ)-induced convulsions. In consideration of such GBP properties, the aim of this work was to investigate its efficacy to protect against sleep disturbances provoked by convulsive seizures induced by the administration of PTZ.Nine-hour (9-hour) polygraphic studies were carried out in chronically implanted male adult Wistar rats separated into 4 different groups of 6 individuals. Control recordings in each group were done after saline administration. One group received a SC Subcutaneous (SC) injection of 50 mg/kg of PTZ alone while the other three groups were injected with either 15, 30, or 60 mg/kg IP Intraperitoneal (IP) of GBP 30 min prior to PTZ (50 mg/kg SC) administration.Animals displayed the whole range of electrophysiological and behavioral manifestations of the disease during the epileptic episodes induced by PTZ administration, and the states of vigilance were significantly altered. Insomnia occurred immediately after PTZ injection preceding the appearance of the first epileptic symptoms. Thus, both slow wave sleep (SWS) and rapid eye movement sleep (REM sleep) were completely inhibited during a relatively long period of time.The disturbing effects of epilepsy on sleep decreased when animals were under GBP treatment. Improvement of sleep was dependent on the administered dose of this antiepileptic drug.

High dose rate brachytherapy as monotherapy for localised prostate cancer

Background and purposeTo evaluate the oncological outcome of a three-implant high dose rate (HDR) brachytherapy (BRT) protocol as monotherapy for clinically localised prostate cancer. Material and methodsBetween February 2008 and December 2012, 450 consecutive patients with clinically localised prostate cancer were treated with HDR monotherapy. The cohort comprised of 198 low-, 135 intermediate- and 117 high risk patients being treated with three single-fraction implants of 11.5Gy delivered to an intraoperative real-time, transrectal ultrasound defined planning treatment volume up to a total physical dose of 34.5Gy with an interfractional interval of 21days. Fifty-eight patients (12.8%) received ADT, 32 of whom were high- and 26 intermediate-risk. Biochemical failure was defined according to the Phoenix Consensus Criteria and genitourinary/gastrointestinal toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 3.0. ResultsThe median follow-up time was 56.3months. The 60-month overall survival, biochemical control and metastasis-free-survival rates were 96.2%, 95.0% and 99.0%, respectively. Toxicity was scored per event with late Grade 2 and 3 genitourinary adverse events of 14.2% and 0.8%, respectively. Late Grade 2 gastrointestinal toxicity amounted 0.4% with no instances of Grade 3 or greater late adverse events to be reported. ConclusionsOur results confirm HDR BRT to be a safe and effective monotherapeutic treatment modality for clinically localised prostate cancer.

A prospective, randomized clinical study comparing drug eluting stent therapy and intranasal corticoid steroid therapy in the treatment of patients with chronic rhinosinusitis.

To conduct the first prospective, randomized controlled clinical trial comparing the efficacy of a drug-eluting stent (DES) (the Relieva StratusTM MicroFlow Spacer) and topical intranasal corticosteroid therapy in patients with chronic rhinosinusitis (CRS). Sixty-three adult patients with ethmoiditis were randomized into either the DES group (n=34) or nasal spray group (n=29). The main outcome variable was the Sinonasal Outcome Test 22, Visual Analogue Scale, nasal endoscopy, rhinometric measurements were performed at the beginning of the study, after three months and six months of follow-up. Both treatments significantly improved quality of the life with no significant difference being found between the two groups. The VAS score decreased in both groups: improvements were significant at three and six months in the nasal spray group, but in the DES group a significant difference was noted only at three months. There was a statistically significant increase in total nasal cavity volumes in the corticosteroid spray group, but not in the DES group. We found that patients benefitted from DES and the corticosteroid nasal spray. We could not find any significant difference between the treatments, except the greater increase in the total nasal cavity volumes favouring the nasal spray group. Because of the very good results for the nasal spray and the much higher material and operating room costs associated with DES, we cannot recommend the use of DES over nasal spray as a monotherapeutic treatment for CRS.

Abstract 306: Antitumor effect of Wee1 inhibitor in gastric cancer cells

Abstract Background: A cell cycle checkpoint is a key step to watch any damages and, it is needed to maintain genomic stability. Thus, to jeopardize cell cycle checkpoint is an attractive strategy for cancer treatment. Wee1 is a G2 cell cycle regulator that phosphorylate cdc2 on tyrosine 15 for inhibiting its activity. The activation of Wee1 can delay G2 phase progression and cells can have a chance to repair DNA damages. Therefore, to inhibit wee1 can accelerate DNA damage accumulation in the cell. AZD1775 is a first-in-class wee1 inhibitor. So far, previous studies showed the antitumor effect of AZD1775 as a mono-therapeutic agent or combination treatment with other chemo-agents. However, the activity of wee1 in gastric cancer (GC) cells is not yet fully understood. Thus, we would like to study whether AZD1775 has an antitumor effect against GC or not. Materials and methods: We determined the antitumor effects of AZD1775 on GC cells using a cytotoxicity assay, cell cycle analysis, immunofluorescence assay and western blotting by AZD1775 treatment. Results: AZD1775 effectively inhibit GC cell proliferation. The TP53 gene status or p-Wee1 expression levels were not associated with AZD1775 sensitivity. AZD1775 effectively down-regulated p-Wee1 and p-cdc2 expressions in SNU-601, a sensitive cell line. However, these effects were not significant in KATO-III cells, which is less sensitive to AZD1775. Cell cycle analysis revealed that the cells had different responses by AZD1775 treatment. SNU-601 cells were enriched in S phase when we decide cell cycle only by its DNA contents. However, KATO-III cells were arrested in G2/M phase. The sub-G1 population was dramatically increased only in SNU-601 cells. A population of BrdU-positive and p-HH3 positive cells was significantly increased in the SNU-601 cells which indicate that premature mitosis was increased. However, no differences were observed in KATO-III cells. Moreover, due to premature mitotic entry, multi-nucleated cells were observed only in SNU-601 cells. Conclusion: AZD1775 effectively inhibited the growth of GC cell lines. The inhibition of cdc2 by AZD1775 was observed only in a sensitive cell line. Moreover, early mitotic entry was induced by AZD1775, and it led the induction of mitotic catastrophe. This result indicates that AZD1775 have an antitumor effect on GC and the possibility of adoption to the clinical trial design. Citation Format: Seongyeong Kim, Ahrum Min, So Hyeon Kim, Dong Hyeon Ha, Hyemin Jang, Yu JIn Kim, Hee Jun Kim, Kyung-Hun Lee, Tae-Yong Kim, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im. Antitumor effect of Wee1 inhibitor in gastric cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 306. doi:10.1158/1538-7445.AM2017-306

Pharmacological and Nonpharmacological Interventions to Arrest Neuroprogression in Psychiatric Disorders.

The concept of neuroprogression describes the progressive course of the disorder and stresses the progressive, recurrent, and chronic course of the disease entity under consideration. It subsumes clinical manifestations of the disease process and may also entail morphological, biochemical, neurochemical, immunological, physiological, and genetic aspects that contribute to the progressive course of the disease in question. In an attempt to identify the appropriate agent or method that could arrest neuroprogression in psychiatric patients, we conducted an evaluation of the use of anti-inflammatory drugs under the perspective of current pharmacological and neurophysiological data. This evaluation included the use of nonsteroidal anti-inflammatory drugs (NSAIDs) as adjunctive treatment to conventional pharmacotherapy as well as the use of natural products exerting anti-inflammatory properties (i.e., ω-3 fatty acids) given as adjunctive or monotherapeutic treatments in less severe cases. The therapeutic significance of nonpharmacological methods, such as psychotherapy, physical exercise, and body-mind therapies, was also considered and will be discussed in this chapter. In conclusion, the role of psychotropic and select anti-inflammatory drugs in arresting neuroprogression is a very promising new frontier in psychiatric research and clinical practice. Modulators of a specific prostanoid synthase or receptor across the cyclooxygenase (COX)-2 downstream pathway along with new multitarget NSAIDs are expected to be tested by the pharmaceutical industry as potential agents to antagonize neuroprogression. Meanwhile, salicylates and selective COX-2 inhibitors could still be used in carefully selected subgroups of patients. Psychotherapy and nonpharmacological, stress-relieving methods should be considered as adjunctive tools to aid in arresting neuroprogression.

A prospective, randomized clinical study comparing drug eluting stent therapy and intranasal corticoid steroid therapy in the treatment of patients with chronic rhinosinusitis

To conduct the first prospective, randomized controlled clinical trial comparing the efficacy of a drug-eluting stent (DES) (the Relieva StratusTM MicroFlow Spacer) and topical intranasal corticosteroid therapy in patients with chronic rhinosinusitis (CRS). Sixty-three adult patients with ethmoiditis were randomized into either the DES group (n=34) or nasal spray group (n=29). The main outcome variable was the Sinonasal Outcome Test 22, Visual Analogue Scale, nasal endoscopy, rhinometric measurements were performed at the beginning of the study, after three months and six months of follow-up. Both treatments significantly improved quality of the life with no significant difference being found between the two groups. The VAS score decreased in both groups: improvements were significant at three and six months in the nasal spray group, but in the DES group a significant difference was noted only at three months. There was a statistically significant increase in total nasal cavity volumes in the corticosteroid spray group, but not in the DES group. We found that patients benefitted from DES and the corticosteroid nasal spray. We could not find any significant difference between the treatments, except the greater increase in the total nasal cavity volumes favouring the nasal spray group. Because of the very good results for the nasal spray and the much higher material and operating room costs associated with DES, we cannot recommend the use of DES over nasal spray as a monotherapeutic treatment for CRS.

Incorporating PARP-inhibitors into clinical routine: A tailored treatment strategy to tackle ovarian cancer

DNA repair mechanisms play a key role in oncogenesis and cancer progression in women with BRCA mutation-positive (BRCAm) ovarian cancer (OC). The BRCA1/2 and poly(ADP-ribose) polymerase (PARP) proteins are considered the foremost mediators among the various components of double-strand and single-strand repair, respectively. A series of new therapeutic drugs that target PARP have been developed for BRCAm OC. This class of agents provokes tumour-specific cytotoxicity with minimal side effects by inducing synthetic lethality, of which they are the first clinical example. The European Medicines Agency granted accelerated licensing approval for the first-in-class-drug that inhibits PARP, olaparib (Lynparza™, AstraZeneca). Olaparib can be used as a monotherapeutic maintenance treatment in patients with platinum-sensitive relapsed (germline and/or somatic) BRCAm high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer responsive to platinum-based chemotherapy. Seen in light of these recent events, this review article will focus on (a) how PARP-inhibitors exploit cancer-specific defects in the homologous recombination repair apparatus and (b) how BRCA testing is implemented in routine clinical care.

Combination of Melatonin and Metformin Hydrochloride for Treatment Polycystic Ovarian in Female Rats

Background: Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder, results in menstrual abnormalities, androgynism and infertility. In the case of women or others animals with PCOS wishing to treat infertility with the aim of becoming pregnant, the most commonly used is metformin hydrochloride. Recent studies have analyzed the combination of metformin hydrochloride with melatonin in oncological treatment but not to treatment of polycystic ovary syndrome (PCOS). The aim of the present study was to analyze the effectiveness of the combination of metformin hydrochloride and melatonin in the treatment of PCOS to improve the fertility of rats and your hormonal alterations.Materials, Methods & Results: This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Federal Rural of Pernambuco (Permit Number: 23081.009130/2010). A total of 50 albino Wistar rats were used. The animal laboratory of an academic research environment, were randomly separated into five groups consisting of 10 females each. After inducing PCOS, the rats were treated with metformin hydrochloride, and/or melatonin, and the results compared with standard and ultrasound confirmed. The physiological similarities were confirmed by our academic researchers morphological science, and published to the association results of effects syndrome induction through constant lighting in reputable magazine recently. This article was analyzed histological of the implantation sites and ovaries, and the estradiol and progesterone levels on the seventh day of gestation, and the other rats for monitoring pregnancy and morphological identification of possible fetal abnormalities, weight measurement and quantification of offspring. The rats were anaesthetized with intraperitoneal injections of ketamine hydrochloride (80 mg/kg) and xylazine (6 mg/kg) to allow analysis of the reproductive organs. Main outcome measures: The study included histopathology, histochemical and quantitative (of the implantation sites) tests, ultrasound analysis, weight benchmarking and ovarian histology tests, as well as comparison of serum estradiol and progesterone levels, and the morphological assessment of offspring. Results paper shows pharmacological treatment reduced the time needed for pregnancy, increased the plasma progesterone levels, the number and weight of offspring, and reduced plasma estrogen levels and collagen fiber grade, improving blastocyst-endometrium interaction and fetal development.Discussion: Our team of researchers confirmed in a previous paper; in addition, the main experimental model used in research about PCOS in recent years, and considered appropriate combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the POS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring. The treatment with a combination of metformin hydrochloride and melatonin was more effective against hormonal alterations produced by PCOS, allowing a normalization of biochemical parameters during pregnancy, than monotherapeutic treatment with these drugs. In conclusion, proposed drug combination is a viable option to treatment of polycystic ovary syndrome and improved fetal development. This article allows suggest that further research should be conducted to examine effects associated with these drugs in the treatment of diseases of the female reproductive system experimentally. Only such treatment later in animals and humans suggest.

The possibilities for the treatment of exudative otitis media in the children presenting with chronic adenoiditis

The objective of the present study was to improve the effectiveness of medicamental therapy of exudative otitis media in the children with recurrent and chronic adenoiditis. It was shown that the use of fluifort (carbocysteine lysine salt) for the treatment of exudative otitis media in the children presenting with chronic adenoiditis is a more effective approach in comparison with the expectant management. It is concluded that the application of carbocysteine lysine salt in combination with the mometasone furoate nasal spray ensures the rapid elimination of the symptoms of adenoiditis and significantly accelerates the resolution of exudative otitis media compared with the monotherapeutic treatment.

Amoebic liver abscess in travellers: indication for image-guided puncture?

Although amoebic liver abscess due to Entamoeba histolytica is one of the most common parasitic infections worldwide, invasive disease remains uncommon in industrialized countries. Metronidazole is the standard of care for complicated and uncomplicated invasive amoebiasis. Puncture of amebic liver abscesses is a treatment option primarily for complicated abscesses (localized in left lobe, multiple, and/or pyogenic abscesses). The role of image-guided percutaneous puncture in initially uncomplicated liver abscess formations still remains unanswered. A subset of patients with uncomplicated amoebic liver abscesses, however, fails to respond to conservative treatment alone. We report two cases of amoebic liver abscess formations in Austrian travelers. Two males, aged 67 and 43, presented with fever, chills and fatigue. Four months prior to admission both patients travelled together to Goa, India, for 4 weeks. Computed tomography showed uncomplicated liver abscess formations and serology for E. histolytica was positive in both patients. Therapy with metronidazole 500 mg four times daily was initiated. Computed tomography then showed an increase in size of liver abscess formations in both patients after 13 and 10 days of intravenous metronidazole therapy, respectively. Patient 1 developed pleural effusion and patient 2 additional liver abscess formations. Therefore CT-guided percutaneous therapeutic catheter drainage of liver abscess formations was performed in both patients without complications. Real time PCR of abscess drainage was positive for E. histolytica in both patients. After completion of metronidazole, paromomycin 500 mg three times daily was initiated for seven days for elimination of cysts and both patients were discharged without further complaints. This report highlights that conservative monotherapeutic treatment alone may not be sufficient in some patients with initially uncomplicated E. histolytica liver abscess. Implementation of additional image guided percutaneous puncture may reduce mortality and disease related costs.

The Continuing Evolution of HIV-1 Therapy: Identification and Development of Novel Antiretroviral Agents Targeting Viral and Cellular Targets

During the past three decades, over thirty-five anti-HIV-1 therapies have been developed for use in humans and the progression from monotherapeutic treatment regimens to today's highly active combination antiretroviral therapies has had a dramatic impact on disease progression in HIV-1-infected individuals. In spite of the success of AIDS therapies and the existence of inhibitors of HIV-1 reverse transcriptase, protease, entry and fusion, and integrase, HIV-1 therapies still have a variety of problems which require continued development efforts to improve efficacy and reduce toxicity, while making drugs that can be used throughout both the developed and developing world, in pediatric populations, and in pregnant women. Highly active antiretroviral therapies (HAARTs) have significantly delayed the progression to AIDS, and in the developed world HIV-1-infected individuals might be expected to live normal life spans while on lifelong therapies. However, the difficult treatment regimens, the presence of class-specific drug toxicities, and the emergence of drug-resistant virus isolates highlight the fact that improvements in our therapeutic regimens and the identification of new and novel viral and cellular targets for therapy are still necessary. Antiretroviral therapeutic strategies and targets continue to be explored, and the development of increasingly potent molecules within existing classes of drugs and the development of novel strategies are ongoing.

Indirect Comparisons of Adverse Events and Dropout Rates in Early Parkinson's Disease Trials of Pramipexole, Ropinirole, and Rasagiline

ABSTRACTThe comparative safety profiles of monotherapeutic treatments for Parkinson's disease (PD) can provide valuable therapeutic information. The objective of this study was to perform an indirect comparison of Adverse Events (AEs) and Dropout Rates (DRs) among clinical trials of pramipexole, ropinirole, and rasagiline. Outcomes analyzed included DRs, total AEs, and AE categories: Cognitive (CG), Gastrointestinal (GI), and Sleep/Fatigue (SF). The odds-ratio (OR) and Credible Interval (CrI) of outcomes between products using placebo as common comparator was calculated using indirect meta-analytical methods. AEs incidences for subjects receiving rasagiline were not significantly different from placebo, whereas DRs were significantly lower than for placebo (OR = 0.55; 95% CrI = 0.34–0.88). Patients receiving pramipexole or ropinirole had higher incidence of all AEs and DRs than patients taking rasagiline, except for the nonsignificant incidence of CG for ropinirole vs. rasagiline (1.76; 0.69–4.70). The incidence of GI (2.11; 1.13–4.06) and SF (2.75; 1.42–5.47) was significantly higher for ropinirole than for pramipexole, whereas the incidence of CG was significantly lower for ropinirole than for pramipexole (0.22; 0.07–0.69). Findings suggest that subjects with early PD treated with rasagiline have fewer AEs and DRs than those treated with pramipexole or ropinirole. GI and SF AEs were highest for subjects treated with ropinirole, while individuals treated with pramipexole exhibited the highest incidence of cognitive AEs.