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1.
BMC Psychiatry ; 24(1): 202, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475754

RESUMO

BACKGROUND: Mental health literacy (MHL) and help-seeking behaviors are pivotal in managing mental well-being, especially among Egyptian undergraduates. Despite the importance and prevalent psychological distress in this group, limited research has addressed MHL and associated behaviors in Egypt. This study aimed to assess the levels of MHL and help-seeking behavior among Egyptian university students. METHODS: A cross-sectional study was conducted across ten Egyptian universities during the academic year 2022-2023. A convenience sample of 1740 students was obtained through online questionnaires distributed via social media platforms. The survey comprised demographic characteristics, the Mental Health Literacy Scale (MHLS), and the General Help Seeking Behavior Questionnaire (GHSPQ). RESULTS: Among 1740 Egyptian undergraduates, medical students scored higher in recognizing disorders (p < 0.05), while non-medical students excelled in attitudes (p < 0.05). A strong correlation was observed between attitudes toward mental illness and total mental health literacy (coefficients of 0.664 and 0.657). Univariate analysis indicated a significant association with professional help-seeking (OR = 1.023). Females, individuals aged 21 or above, and non-medical students were more likely to seek mental health information (OR = 1.42, 1.82, 1.55 respectively). Help-seeking behavior for emotional problems was more inclined towards intimate partners, whereas suicidal thoughts prompted seeking professional help. CONCLUSION: The findings advocate for comprehensive mental health education, particularly in rural areas, and emphasis on the role of personal relationships in mental well-being. Implementing these insights could foster improved mental health outcomes and reduce related stigma in Egypt.


Assuntos
Letramento em Saúde , Comportamento de Busca de Ajuda , Transtornos Mentais , Feminino , Humanos , Saúde Mental , Estudos Transversais , Egito , Estudantes/psicologia , Transtornos Mentais/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Estigma Social
2.
3.
Allergy Asthma Clin Immunol ; 20(1): 15, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388670

RESUMO

BACKGROUND: While a connection has been established between serum interleukin-6 (IL-6) levels and the IL-6 gene (- 174G/C) polymorphism in allergic diseases such as asthma, its specific association with severe asthma remains unexplored. This study examined the relationship between the IL-6 (- 174G/C) gene polymorphism and mild and severe asthma, focusing on its influence on type 2 inflammation. METHODS: Our study comprised 98 patients with mild asthma and 116 with severe asthma. Additionally, we recruited 121 healthy participants to serve as controls for comparative analyses. The IL-6 gene (- 174G/C) polymorphism was assessed utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In our study, the risk of mild asthma exhibited a significant fourfold increase in individuals with the GG genotype pattern compared to healthy controls, yielding an odds ratio (OR) of 4.4 (p < 0.001). Conversely, we found no significant correlation between the IL-6 - 174G/C gene polymorphism and severe asthma when compared to the healthy control group. However, a noteworthy pattern emerged when we compared subgroups of mild and severe asthma. The risk of severe asthma increased fivefold in individuals with the GC polymorphism pattern, with an OR of 4.99 (p < 0.001), while the likelihood of mild asthma showed a similar fourfold increase with the GG polymorphism pattern, OR = 4.4 (p < 0.001). Consequently, we observed a significantly higher frequency of the C allele in patients with severe asthma, whereas the G allele was more prevalent in individuals with mild asthma (p = 0.05). Additionally, the correlation between markers of type 2 inflammation and the dominant model of the IL-6 gene -174G/C polymorphism (CC + CG vs GG) revealed a significant increase in total serum immunoglobulin E (IgE), Blood Eosinophil Counts (BEC), and Fractional Exhaled Nitric Oxide (FeNO) levels in asthmatic patients with the CC + CG gene pattern compared to those with GG, with p-values of 0.04, 0.03, and 0.04, respectively. Furthermore, after adjusting for other risk factors, the likelihood of developing severe asthma increased from fourfold to eightfold, with an OR of 8.12 (p = 0.01) with (CC + CG) gene pattern. Other predictors for severe asthma included older age and childhood-onset disease (OR = 1.13 and 19.19, p < 0.001). Allergic rhinitis (AR) and nasal polyps (NP) also demonstrated a substantial association with an increased risk of severe asthma, with odds ratios of 5 and 32.29 (p = 0.01 and < 0.001), respectively. Additionally, elevated Body Mass Index (BMI), BEC, and FeNO were linked to severe asthma, with ORs of 1.11, 1.00, and 1.04, respectively (p = 0.04, 0.05, and 0.001). CONCLUSION: This study illuminated the intricate relationship between the IL-6 gene polymorphism, type 2 inflammation markers, and diverse risk factors in shaping asthma severity. As a significant association between the GG polymorphism of the IL-6 gene (- 174G/C) and mild asthma was found, while possessing at least one C allele, whether in a homozygous (CC) or heterozygous (CG) combination, independently predicts the likelihood of severe asthma.

4.
J Pediatr Surg ; 59(2): 192-196, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38016850

RESUMO

AIM OF THE STUDY: We describe the short- and medium-term outcomes following open and laparoscopic assisted oesophageal replacement surgery in a single tertiary paediatric surgical centre. METHODS: A retrospective review (institutional audit approval no. 3213) on patients who underwent open or laparoscopic-assisted oesophageal replacement (OAR vs. LAR) at our centre between 2002 and 2021 was completed. Data collected (demographics, early complications, stricture formation, need for oesophageal dilatations, and mortality) were analysed using GraphPad Prism v 9.50 and are presented as median (IQR). RESULTS: 71 children (37 male) had oesophageal replacement surgery at a median age of 2.3 years (IQR 4.7 years). 51 were LAR (6 conversions). Replacement conduit was stomach (n = 67), colon (n = 3), or jejunum (n = 1). Most gastric transpositions had a pyloroplasty (46/67) or pyloromyotomy (14/67). Most common pathology was oesophageal atresia (n = 50 including 2 failed transpositions), caustic injury (n = 19 including 3 due to button battery), stricture of unknown cause (n = 1), and megaoesophagus (n = 1). There were 2 (2.8 %) early postoperative deaths at 2 days (major vessel thrombosis), 1 month (systemic sepsis), and one death at 5 years in the community. The rate of postoperative complications were comparable across LAR and OAR including anastomotic leak, pleural effusions, or early strictures. More patients with caustic pathology needed dilatations (60 % vs 30 % in OA, p = 0.05). CONCLUSIONS: Outcomes of open and laparoscopic-assisted oesophageal replacement procedures are comparable in the short and medium term. Anastomotic stricture is higher in those with caustic injury. LEVEL OF EVIDENCE: IV.


Assuntos
Cáusticos , Atresia Esofágica , Estenose Esofágica , Laparoscopia , Criança , Humanos , Masculino , Pré-Escolar , Estenose Esofágica/epidemiologia , Estenose Esofágica/etiologia , Estenose Esofágica/cirurgia , Constrição Patológica/cirurgia , Atresia Esofágica/cirurgia , Atresia Esofágica/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Laparoscopia/métodos , Estudos Retrospectivos
5.
BMC Pulm Med ; 23(1): 490, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053108

RESUMO

BACKGROUND: A significant breakthrough has been made in treating severe asthma, with the recognition of various asthma phenotypes and an updated management guideline. Type 2 targeted therapies, such as benralizumab and omalizumab; have been identified as an effective treatment for severe asthma, improving patient response, lung function tests and asthma symptom control. This study aimed to evaluate factors contributing to poor response to therapy. METHODS: A retrospective single-center cohort study of 162 patients with severe asthma who started biologic therapy; their data were retrieved from medical records for further analysis. Poor responders were patients remained clinically and functionally uncontrolled despite even after augmenting all treatment options. RESULTS: Childhood-onset asthma, bronchiectasis, poor symptom control (ACT below 19), severe airway obstruction (< 60% predicted), and maintenance oral corticosteroid (mOCS) use were significantly associated with poor response to omalizumab and benralizumab; p = 0.0.4 and 0.01; 0.003 and 0.01; 0.01 and 0.001, 0.05 and 0.04; 0.006 and 0.02, respectively. However, chronic rhinosinusitis and IgE < 220kIU/L were associated with higher poor response rates to omalizumab (p = 0.01 and 0.04, respectively). At the same time, female patients and those with blood eosinophils level < 500 cells/mm3 had a higher poor response rate to benralizumab (p = 0.02 and 0.01, respectively). Ischemic heart disease (IHD), bronchiectasis, and continued use of OCS increased the likelihood of poor response to omalizumab by 21, 7, and 24 times (p = 0.004, 0.008, and 0.004, respectively). In contrast, the female gender, childhood-onset asthma and higher BMI increased the likelihood of poor response to benralizumab by 7, 7 and 2 times more, p = 0.03, 0.02 and 0.05, respectively. CONCLUSION: Poor response to omalizumab treatment was independently associated with ischemic heart disease (IHD), bronchiectasis, and a history of maintenance oral corticosteroid (mOCS) use. Conversely, poor response to benralizumab therapy was independently linked to female gender, childhood-onset asthma and higher body mass index (BMI).


Assuntos
Antiasmáticos , Asma , Bronquiectasia , Isquemia Miocárdica , Humanos , Feminino , Criança , Omalizumab/uso terapêutico , Antiasmáticos/uso terapêutico , Estudos Retrospectivos , Estudos de Coortes , Imunoglobulina E , Corticosteroides/uso terapêutico
6.
Trop Dis Travel Med Vaccines ; 9(1): 22, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38001495

RESUMO

BACKGROUND: The American Society of Haematology defines immune thrombocytopenic purpura (ITP) as a common hematologic disorder characterized by a transient or long-term decrease in platelet counts (< 100 × 109/L.), purpura, and haemorrhagic episodes caused by antiplatelet autoantibodies, with the exclusion of other clinical conditions. We aimed to systematically determine the incidence of ITP in adults and children following influenza vaccination, the duration between vaccination and the occurrence of ITP, and to identify predictors of ITP after the vaccine. METHODS: We searched PubMed, Cochrane Library, Google Scholar, Web of Science, Scopus, and Science Direct. We included primary studies that assessed the occurrence of immune thrombocytopenia in individuals who had received any influenza vaccine (primary or booster dose), regardless of the dosage, preparation, time of administration, or age of the participants. We excluded studies that were (a) Narrative, scoping, and umbrella reviews ;(b) studies with no accessible full text, abstract-only studies, or (c) Overlapping or unreliable data. The risk of bias in the included studies was assessed using the Joanna Briggs Institute (JBI) tool. We categorized studies for qualitative analysis based on study design. Descriptive statistics were used to summarize quantitative data, including the incidence of ITP after influenza vaccination. RESULTS: Out of 729 articles retrieved from the database search, we included 24 studies. All patients identified and included in this systematic review presented with immune thrombocytopenia, determined by their platelet count. The period between vaccination and the occurrence of ITP ranged from (2:35 days). The mean duration was 13.5 days. The analysis revealed a statistically significant incidence rate ratio (IRR) = 1.85,95% CI [1.03-3.32] of ITP occurrence after 42 days. CONCLUSIONS: Influenza-associated ITP is uncommon, self-limiting, non-life-threatening, and curable. None of the patients reported having severe adverse events or death. Further studies are required to confirm the exact incidence of the ITP to better understand the pathophysiology of ITP development post-influenza vaccination.

7.
Med Princ Pract ; 32(6): 323-331, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37757780

RESUMO

OBJECTIVE: The objective of this study was to assess the effectiveness of switching from omalizumab to another biologic therapy for patients with severe asthma and evaluate factors that influenced the decision to switch and determined the optimal time for a good biologic response. SUBJECTS AND METHODS: A retrospective study of severe asthma patients was conducted at Al-Rashed Allergy Center, a tertiary center in Kuwait. After meeting the eligibility criteria, patients were divided into two comparative groups: those continuing with omalizumab and those who started with omalizumab but switched to another biologic. RESULTS: One hundred sixteen patients with severe asthma were recruited, and only 33 had access to multiple biological treatments. Approximately 22.4% switched from omalizumab. Male patients with a history of ischemic heart disease, chronic rhinosinusitis, and nasal polyps were more likely to switch if they had higher levels of eosinophils in the sputum. This study showed that every 1% increase in sputum eosinophils doubled the likelihood of a switch. Patients with access to alternative biological options had a much shorter mean duration of omalizumab therapy before switching compared to those with only affordable omalizumab: 4.9 ± 1.5 years versus 8.9 ± 1.3 years (p < 0.001). The optimal time to predict the likelihood of a good response was less than 5.5 years, with an area under the curve of 0.91 and p = 0.003. This cutoff point provided a sensitivity and specificity of approximately 89% and 100%, respectively. CONCLUSION: An early transition from omalizumab, specifically within the first 5 years of treatment, in patients with severe asthma and higher sputum eosinophils may enhance the likelihood of a good response if other biological therapies were available.


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Humanos , Masculino , Omalizumab/uso terapêutico , Estudos Retrospectivos , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Resultado do Tratamento
9.
J Orofac Orthop ; 84(2): 88-99, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34414482

RESUMO

OBJECTIVE: To investigate the effect of enamel deproteinization and air abrasion on shear bond strength (SBS), adhesive remnant index (ARI) scores, and surface topography when bonding orthodontic brackets to fluorosed enamel. MATERIALS AND METHODS: The sample included 90 fluorosed and 30 normal premolars divided into four groups: group I (fluorosed premolars subjected to air abrasion before acid etching), group II (fluorosed premolars subjected to deproteinization before acid etching), group III (fluorosed premolars; control for groups I and II), and group IV (normal premolars; control for group III). Bonding procedures included etching with 37% phosphoric acid, priming with TransbondTM XT primer (3M Unitek, Monrovia, CA, USA), and application of TransbondTM XT adhesive paste (composite; 3M Unitek, Monrovia, CA, USA). Air abrasion was done using 50 µm aluminum oxide particles under 0.28 MPa pressure for 5 s with the micro-etcher held at a distance of 10 mm. Deproteinization was done for 60 s with 5% sodium hypochlorite (NaOCl). RESULTS: Fluorosed premolars subjected to deproteinization showed the lowest (median = 6.57 MPa) SBS among the four groups, followed by 8.14, 8.90, 8.14 MPa for groups I, III, and IV respectively. ARI scores were significantly different between the four groups (p = 0.006). Fluorosed enamel etched after air abrasion or deproteinization with NaOCl showed a predominance of type 4 etching pattern with some areas appearing unetched. CONCLUSIONS: Shear bond strength of all groups was within the 6-8 MPa acceptable range for orthodontic purposes. Fluorosed premolars subjected to deproteinization showed the lowest values. Further studies are recommended to scrutinize the deproteinization technique.


Assuntos
Colagem Dentária , Braquetes Ortodônticos , Cimentos de Resina/química , Propriedades de Superfície , Abrasão Dental por Ar , Condicionamento Ácido do Dente/métodos , Colagem Dentária/métodos , Análise do Estresse Dentário , Teste de Materiais , Esmalte Dentário , Resistência ao Cisalhamento
10.
AMB Express ; 12(1): 147, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36434306

RESUMO

Giardia duodenalis (G. duodenalis) is an infectious protozoan that has a global distribution especially in the hot climate. Around 200 million people are infected worldwide annually by Giardia, but infection is not always accompanied by symptoms, especially in endemic countries. Using traditional microscopy techniques in diagnosis, both in stool and water samples were less sensitive when compared to immunological methods; and the need for new diagnostic methods was necessary. Also, protection from infection is required in endemic areas. Therefore, the study aimed to produce anti- G. duodenalis IgG polyclonal antibodies (pAbs) by immunizing rabbit by G. duodenalis cyst recombinant protein. The produced antibodies were evaluated in the detection of G. duodenalis antigens in patients' stool and water samples from endemic areas across River Nile; where pAbs were used as a coating and a peroxidase conjugate antibody in sandwich ELISA. Moreover, pAbs were tested for the protection of mice from giardiasis. Sandwich ELISA using pAb has succeeded in the detection of G. duodenalis coproantigens in stool samples by a sensitivity of 97% and a specificity of 92.72%. Moreover, G. duodenalis cyst was detected in only seven water samples by ordinary microscopy; while sandwich ELISA revealed nineteen positive results. IgG pAb (1/200 µg/ml) protected mice from giardiasis; which was evident from the reduction in cysts and trophozoites numbers. We recommended the use of sandwich ELISA to monitor water quality, investigate environmental contamination and diagnosis in patients' stools. The pAbs can be prepared in large amount and used in field diagnosis and protection. This will help in the early diagnosis of G. duodenalis in water, which in turn can control outbreaks in rural areas.

11.
Pak J Biol Sci ; 25(6): 485-494, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36098183

RESUMO

<b>Background and Objective:</b> For more than a decade, breast cancer has been one of the most common forms of cancer among women around the world. The present article aimed to evaluate the protective activity of CEG-AgNPs against DMBA-induced mammary carcinoma. <b>Materials and Methods:</b> In this experimental study, green synthesis and characterization of CEG-AgNPs were carried as well as IC<sub>50</sub> against Mcf7 cell line and LD<sub>50</sub> on mice were evaluated. A total of 24 adult albino mice were divided into four groups six rats in each. Group I was given an equal amount of distilled water, group II was received 80 mg kg<sup></sup><sup>1</sup> b.wt., DMBA for 4 weeks, groups III and IV were treated with CEG-AgNPs (28.1 and 70.25 mg kg<sup></sup><sup>1</sup>) from the 5th week of DMBA administration for 4 weeks, respectively. <b>Results:</b> CEG-AgNPs were approximately 42.32±9.52 nm with a negative zeta potential of -17.44. It is IC<sub>50</sub> against the Mcf7 cell line and LD<sub>50</sub> is equal to 82.76 µg mL<sup></sup><sup>1</sup> and 1405 mg kg<sup></sup><sup>1</sup> b.wt., A significant normalization in plasma ALT, AST, AST and LDH as well as mammary MDA, TNF-α, IL-6, P53, SOD, GPx and GSH levels have been observed in CEG-AgNPs treated mice. Oral CEG-AgNPs administration has suppressed VEGF-C gene expression in DMBA-treated mice. <b>Conclusion:</b> The present results, biochemical, histological and MRI results showed that CEG-AgNPs have potent anticancer activity against DMBA-induced mammary carcinoma in mice by inducing the biosynthesizes of antioxidant biomarkers and suppression of cytokines gene expression.


Assuntos
Carcinoma , Neoplasias Mamárias Experimentais , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Antioxidantes , Citocinas , Feminino , Humanos , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/prevenção & controle , Camundongos , Ratos
12.
Int J Surg Case Rep ; 90: 106647, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34979425

RESUMO

INTRODUCTION: Splenic tumours are relatively rare and include malignancies such as lymphomas, angiosarcomas, plasmacytomas, primary malignant fibrous histiocytomas, and splenic metastases. Benign tumours of the spleen such as hemangiomas, cysts, and inflammatory pseudotumours are very rare (Kaza et al., 2010, PisaniCeretti et al., 2012) [1,2]. There are fewer than 160 cases of splenic hamartoma or splenomas having been reported in the literature (Basso et al., 2012) [3]. Only 20% of the cases were detected in children (Abramowsky et al., 2004) [4]. Although multi-modality imaging findings were described preoperatively, the final diagnosis was splenic hamartoma based on histology and immunohistochemistry. CASE REPORT: Here, we report a case of a14 year old child left upper quadrant abdominal pain and worsening sickness. Multi-modality imaging detected a solid lesion of the spleen, who required splenectomy and was pathologically diagnosed as a splenic hamartoma. The postoperative course was uneventful. DISCUSSION: Splenic hamartoma is very rare. Only 20% of hamartomas occur in children. They are commonly found incidentally on imaging with no symptoms. CONCLUSION: Splenic hamartoma is a benign vascular proliferative lesion that requires a multi-modality imaging studies for diagnosis and confirmed by histopathology. It must be included in the differential diagnosis of splenic mass forming lesions.

13.
J Contemp Dent Pract ; 23(11): 1111-1121, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37073934

RESUMO

AIMS: To compare skeletal, dentoalveolar, and soft tissue changes between Twin block and early fixed orthodontic appliance for class II division 1 malocclusion treatment through a randomized controlled trial. MATERIALS AND METHODS: Sample and randomization: This study was a randomized controlled trial with a 1:1 allocation ratio in which 40 patients were divided equally into two groups: control and experimental; each group had an equal number of boys and girls. Randomization was achieved using random blocks of 20 patients with allocation concealed in sequentially numbered, opaque, and sealed envelopes. Blinding was only applicable for data analysis of radiographic measurements. Intervention: Twin block appliance was used in the experimental group for 1 year. However, control group was treated with fixed appliance. Inclusion criteria: Skeletal class II division 1 malocclusion with mandibular retrognathism; cephalometric angular measurements: SNA ≥ 82, SNB ≤ 78, ANB ≥ 4; overjet ≥6 mm; and patient in circumpubertal stage cervical vertebral maturation (CVM2 and CVM3). Parameters for evaluation: Cephalometric skeletal, dental, and soft tissue angular and linear measurements were used for evaluation. RESULTS: SNB increased remarkably by 4° in the Twin block group, but only by 0.68 in the control group. There was a significant decrease in vertical dimensions (SN-GoGn) in the Twin block group compared to control group (p = 0.002). Significant enhancement in the facial profile of the patients was observed. CONCLUSIONS: The Twin block appliance induced significant skeletal and dental changes. These changes were more obvious relative to the slight changes induced by natural growth. CLINICAL SIGNIFICANCE: Early treatment of Class II due to mandibular retrusion with Twin block functional appliance is recommended due to its favourable skeletal effect. Early treatment with fixed appliance affects mainly the dentoalveolar component. Long term follow-up is needed for further insights.


Assuntos
Má Oclusão Classe II de Angle , Má Oclusão , Aparelhos Ortodônticos Funcionais , Masculino , Feminino , Humanos , Mandíbula/diagnóstico por imagem , Má Oclusão Classe II de Angle/diagnóstico por imagem , Má Oclusão Classe II de Angle/terapia , Ossos Faciais , Cefalometria/métodos , Aparelhos Ortodônticos Fixos , Resultado do Tratamento
14.
CNS Neurol Disord Drug Targets ; 21(7): 631-639, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34397335

RESUMO

BACKGROUND: Over the last few years, the number of people suffering from sleeping disorders has increased significantly despite negative effects on cognition and an association with brain inflammation. OBJECTIVES: We assessed memory deficits caused by Sleep Deprivation (SD) to determine the therapeutic effect of phosphodiesterase 4 (PDE4) inhibitors on SD-induced memory deficits and to investigate whether the modulation of memory deficits by PDE4 inhibitors is mediated by a protein kinase A (PKA)-independent pathway in conjunction with a PKA-dependent pathway. METHODS: Adult male mice were divided into four groups. Three SD groups were deprived of Rapid Eye Movement (REM) sleep for 12 h a day for six consecutive days. They were tested daily in the Morris water maze to evaluate learning and memory. One of the SD groups was injected with a PDE4 inhibitor, rolipram (1 mg/kg ip), whereas another had rolipram co-administered with chlorogenic acid (CHA, 20 mg/kg ip), an inhibitor of PKA. After 6 days, the mice were sacrificed, and the hippocampi were evaluated for cyclic AMP (cAMP) and nuclear factor Nrf-2 levels. The hippocampal expression of PKA, phosphorylated cAMP Response Element-Binding Protein (CREB), and phosphorylated glycogen synthase 3ß (Ser389) were also evaluated. RESULTS: SD caused a significant decrease in cAMP levels in the brain and had a detrimental effect on learning and memory. The administration of rolipram or rolipram+CHA resulted in an improvement in cognitive function. CONCLUSION: The present study provides evidence that restoration of memory with PDE4 inhibitors occurs through a dual mechanism involving the PKA and Epac pathways.


Assuntos
Consolidação da Memória , Inibidores da Fosfodiesterase 4 , Animais , AMP Cíclico/metabolismo , AMP Cíclico/uso terapêutico , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/uso terapêutico , Fatores de Troca do Nucleotídeo Guanina/uso terapêutico , Humanos , Masculino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Camundongos , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Rolipram/farmacologia , Rolipram/uso terapêutico , Privação do Sono/complicações , Privação do Sono/tratamento farmacológico
15.
Bioorg Chem ; 117: 105422, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34700110

RESUMO

The emergence of bacterial resistance has triggered a multitude of efforts to develop new antibacterial agents. There are many compounds in literature that were reported as potent antibacterial agents, however, they lacked the required safety to mammalian cells or no clear picture about their toxicity profile was presented. Inspired by discovered hit from our in-house library and by previously reported 2,4-diaminosubstituted quinazolines, we describe the design and synthesis of novel 2,4-disubstituted-thioquinazolines (3-13 and 36), 2-thio-4-amino substituted quinazolines (14-33) and 6-substituted 2,4-diamonsubstituted quinazolines (37-39). The synthesized compounds showed potent antibacterial activity against a panel of Gram-positive, efflux deficient E.coli and Mycobacterium smegmatis. The panel also involved resistant strains including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Enterococcus faecium, in addition to Mycobacterium smegmatis. The newly synthesized compounds revealed MIC values against the tested strains ranging from 1 to 64 µg/mL with a good safety profile. Most of the 2-thio-4-amino substituted-quinazolines showed significant antimycobacterial activity with the variations at position 2 and 4 offering additional antibacterial activity against the different strains. Compared to previously reported 2,4-diaminosubstituted quinazolines, the bioisosteric replacement of the 2-amino with sulfur offered a successful approach to keep the high antibacterial potency while substantially improving safety profile as indicated by the reduced activity on different cell lines and a lack of hemolytic activity.


Assuntos
Antibacterianos/farmacologia , Quinazolinas/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Cricetulus , Relação Dose-Resposta a Droga , Enterococcus faecalis/efeitos dos fármacos , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium smegmatis/efeitos dos fármacos , Quinazolinas/síntese química , Quinazolinas/química , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Relação Estrutura-Atividade
16.
Respir Med ; 187: 106586, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34474336

RESUMO

BACKGROUND: There is increasing recognition of marked phenotypic heterogeneity within severe asthma patients. METHODS: Severe asthma patients on GINA step 4 or 5 treatment, followed up at Al-Rashed Allergy center Kuwait, were evaluated for: demographics (gender, age, age of asthma onset), comorbidities (allergic rhinitis (AR), chronic rhinosinusitis (CRS), chronic rhinosinusitis with nasal polyposis (CRSwNP), obesity), blood biomarkers (total serum Immunoglobulin E (IgE), peripheral eosinophils), and sensitization to inhalants allergens. RESULTS: A total of 169 patients were candidates for biological treatment. Patients were divided in two groups based on level of total IgE as a "low" group with IgE<160 IU/ml (n = 55) and "high" group with IgE≥ 160 IU/ml (n = 114). Both groups were further divided in subgroups, "low" and "high", based on absolute number of eosinophils (Eos) in peripheral blood with <300 cells/µl or ≥ 300 cells/µl. Only 10% of patients were in low IgE/low Eos while majority (46%) were in the high IgE/high Eos group. Mean age of patients was 44.1 year with domination of females (n = 123). Majority of patients were obese. AR, CRS and CRSwNP were more common in group with IgE ≥160 IU/ml, while CRS and CRSwNP in group with Eos ≥300 cells/µl. CONCLUSION: The majority of severe asthma patients in Kuwait are obese females with adult-onset asthma (>18 years of age) who were allergic with comorbid conditions including AR, CRS and CRSwNP, which correlates well with the level of Eos.


Assuntos
Asma/epidemiologia , Asma/genética , Fenótipo , Adulto , Alérgenos/imunologia , Asma/imunologia , Comorbidade , Estudos Transversais , Demografia , Eosinófilos , Feminino , Humanos , Imunoglobulina E/sangue , Kuweit/epidemiologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/epidemiologia , Obesidade/epidemiologia , Gravidade do Paciente , Rinite/epidemiologia , Sinusite/epidemiologia , Adulto Jovem
17.
Int J Surg Case Rep ; 86: 106228, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34419723

RESUMO

INTRODUCTION: Human tails are rare congenital malformations that describe protrusions commonly located around the midline of the lumbosacral region covered by skin, representing an embryonic remnant. Human tails are broadly classified into true and pseudo-tails. The real ones represent the persistence of a remnant of the embryonic tail formed between the fourth and eighth week of gestation. PRESENTATION: A male infant aged 42 days presented to our institution with a tail-like structure that originated from the anal mucocutaneos junction. The parents did not bring the baby at birth because of the social stigma and ignorance. On examination, there was a tail-like structure that is about 22 cm in length and 1.5 cm in diameter originated from the mucocutaneous junction at the anus at the left side. There was no bony element on palpation. The lower vertebral column examination showed no abnormalities, and this was confirmed with an x-ray. The patient was operated on with simple excision of the tail and primary closure of the wound at the base. He was discharged on the same day well and good. The tail was taken for microscopic histopathology. DISCUSSION: There are few reported cases describing human tails. However, none of them was originating from the anal mucocutaneous junction. CONCLUSION: We report the first case of a human tail arising from the anal mucocutaneous junction worldwide. Due to its very superficial origin, it was not associated with any other anomalies.

18.
J Med Chem ; 64(8): 4462-4477, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33793216

RESUMO

A ligand-based approach involving systematic modifications of a trisubstituted pyrazoline scaffold derived from the COX2 inhibitor, celecoxib, was used to develop novel PDE5 inhibitors. Novel pyrazolines were identified with potent PDE5 inhibitory activity lacking COX2 inhibitory activity. Compound d12 was the most potent with an IC50 of 1 nM, which was three times more potent than sildenafil and more selective with a selectivity index of >10,000-fold against all other PDE isozymes. Sildenafil inhibited the full-length and catalytic fragment of PDE5, while compound d12 only inhibited the full-length enzyme, suggesting a mechanism of enzyme inhibition distinct from sildenafil. The PDE5 inhibitory activity of compound d12 was confirmed in cells using a cGMP biosensor assay. Oral administration of compound d12 achieved plasma levels >1000-fold higher than IC50 values and showed no discernable toxicity after repeated dosing. These results reveal a novel strategy to inhibit PDE5 with unprecedented potency and isozyme selectivity.


Assuntos
Celecoxib/química , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/química , Inibidores da Fosfodiesterase 5/química , Pirazóis/química , Animais , Proteínas Sanguíneas/química , Proteínas Sanguíneas/metabolismo , Celecoxib/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Desenho de Fármacos , Feminino , Meia-Vida , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microssomos Hepáticos/metabolismo , Inibidores da Fosfodiesterase 5/metabolismo , Ligação Proteica , Pirazóis/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Estereoisomerismo , Relação Estrutura-Atividade
19.
Drug Deliv ; 28(1): 826-843, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33928836

RESUMO

Ciclesonide (CIC), an inhaled corticosteroid for bronchial asthma is currently available as metered dose inhaler (CIC-MDI) which possesses a major challenge in the management of the elderly, critically ill patients and children. In this work, nebulized CIC nano-structure lipid particles (CIC-NLPs) were prepared and evaluated for their deep pulmonary delivery and cytotoxicity to provide additional clinical benefits to patients in controlled manner and lower dose. The bio-efficacy following nebulization in ovalbumin (OVA) induced asthma Balb/c mice compared to commercial (CIC-MDI) was also assessed. The developed NLPs of 222.6 nm successfully entrapped CIC (entrapment efficiency 93.3%) and exhibited favorable aerosolization efficiency (mass median aerodynamic diameter (MMAD) 2.03 µm and fine particle fraction (FPF) of 84.51%) at lower impactor stages indicating deep lung deposition without imparting any cytotoxic effect up to a concentration of 100 µg/ml. The nebulization of 40 µg dose of the developed CIC-NLPs revealed significant therapeutic impact in the mitigation of the allergic airways inflammations when compared to 80 µg dose of the commercial CIC-MDI inhaler (Alvesco®). Superior anti-inflammatory and antioxidative stress effects characterized by significant decrease (p< .0001) in inflammatory cytokines IL-4 and 13, serum IgE levels, malondialdehyde (MDA), nitric oxide (NO), TNF-α, and activated nuclear factor-κB (NF-κB) activity were obvious with concomitant increase in superoxide dismutase (SOD) activity. Histological examination with inhibition of inflammatory cell infiltration in the respiratory tract was correlated well with observed biochemical improvement.


Assuntos
Anti-Inflamatórios/farmacocinética , Pulmão/metabolismo , Nebulizadores e Vaporizadores , Pregnenodionas/farmacocinética , Administração por Inalação , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Linhagem Celular , Sobrevivência Celular , Relação Dose-Resposta a Droga , Liberação Controlada de Fármacos , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Tamanho da Partícula , Pregnenodionas/administração & dosagem , Pregnenodionas/farmacologia , Propriedades de Superfície
20.
Int J Surg Case Rep ; 81: 105769, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33820736

RESUMO

INTRODUCTION: We present a case of a male child 8 years old presenting with a sigmoid volvulus causing ischemia of most of bowel loops resulting in a short bowel syndrome. It is the first reported case worldwide. PRESENTATION: A male child presented with a picture of intestinal obstruction. After complete laboratory and radiological investigation, laparotomy was done revealing a sigmoid volvulus compessing most of the small bowel loops with gangrenous sigmoid colon for which sigmoidectomy with end colostomy, resection of gangrenous small bowel loops and primary anastomosis of the remaining healthy part. DISCUSSION: There are few reported cases describing sigmoid volvulus in this age group. However, none of them resulted in short bowel syndrome. The median age was 7 years with a higher ratio in males than females (3.5:1). CONCLUSION: Sigmoid volvulus is not a common problem in children and adolescents, and is rarely considered as a cause of intestinal obstruction and it was never reported as a cause of short bowel syndrome. Early diagnosis and prompt treatment confer an excellent prognosis.

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