Background: After the closure of patent processus vaginalis (PPV) in boys with indirect inguinal hernia (IIH) or hydrocele, large scrotal hydroceles can occur on rare occasions despite the complete occlusion of internal inguinal ring (IIR). We presen... t some cases that may help to explain the cause of this rare occurrence.
Materials: During last 14 years, six boys exhibited non-communicating large scrotal hydroceles (2 right, 1 left, 3 bilateral) among 352 children who underwent laparoscopic repair for hydroceles. Ages ranged from 7 months to 15 years with a median of 12 years. Five of them had a history of repair for hydrocele or IIH prior to the definitive surgery and one boy underwent an initial operation.
Results: In all the patients, laparoscopic inspection at the definitive surgery revealed completely closed IIRs. One infant with primary hydroceles was found to have large hydroceles bulging into the peritoneal cavity. All the patients were treated with subtotal removal of the sac without any recurrence. Marked thickness of the sack walls with abundant lymph vessels was characteristic histopathological findings.
Conclusions: The complete occlusion of the PPV does not always prevent the recurrence of hydrocele through alternative pathogenesis. The pathological findings of resected specimens suggested a disturbance in lymph flow in the testicular system. The subtotal removal of the sac is the treatment of choice. Diagnostic laparoscopy prior to a direct cut-down approach to the neck of the seminal cord is advisable to identify non-communicating hydroceles to avoid further impairment of lymph drainage around the IIR.Show more >
In the actual medical therapy of BPH, we can see: antibiotics, alpha blockers, 5-ARI, fitotherapeutics/natural products (Serenoa repens) with different which display clinical activities and other molecules such as FANS (local or systemic dosage forms... ) cortisones and others. Relationship between immune systems and chronic prostatitis are strictly involved in BPH progression. A vicious cycle that involve chronic flogosis, tissue remodeling, grow factors, inhibition of apoptosis, and other phenomena. Observing BPH pathogenesis under an immunologic point of view make possible to search new pharmacological strategies, to improve actual therapy.
The aim of this work is to observe some relevant literature in our opinion related the management of BHP and its progression under a pharmaceutical and immunological point of view. A deep knowledge in the pharmaceutical properties of some molecules (antimicrobials, anti-phlogosis agents, Anti-androgenic agents, alpha blockers, 5-ARI and other treatments, techniques, interventions or instruments) can help the physicians to pick the right choice.Show more >
Growing evidence supports the hypothesis that endothelial cell-derived microparticles (MPs) might contribute to the pathogenesis of cardiovascular (CV) disease. Endothelial cell-derived MPs play a pivotal role in the regulation of the endogenous repa... ir system, thrombosis, coagulation, inflammation, immunity and metabolic memory phenomenon. There is evidence that the MPs are secreted actively accompanied to other regulatory molecules. All these actively synthetizing and secreting factors include proteins, adhesion and intercellular signal molecules, peptides, lipids, free DNAs, microRNAs, and even microparticles (MPs) are defined as cellular secretome. The proteomic profile of secretome is under tightly control of genetic and epigenetic mechanisms, which may altered a secretion of the proteins involved into MPs’ organization. Finally, this may contribute the modification of MP’s after their secretion and throughout transfer to the target cells. As a result, communicative ability of endothelial cell-derived MPs may sufficiently worse. Subsequently, cross talk between some components of secretome might modulate delivering cargos of MPs and their regenerative and proliferative capabilities via intercellular signaling networks. The aim of the review is to discuss the effect of various components of secretome on MP-dependent effects on endothelium.Show more >
In the cardiovascular field, tachycardia and increment of catecholamine plasma levels (sympathetic hyperactivity) have been reported by hypertensive patients that use L-type Ca2+ channel blockers (CCBs) since 70´s. Our discovery of the involvement of... interaction between the intracellular signalling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP interaction) revealed that this phenomenon (sympathetic hyperactivity) was resulting of increase of transmitter release from sympathetic neurons stimulated by CCBs due to its interference on the Ca2+/cAMP interaction. In the neuroscience field, this discovery has produced new paths for the understanding of the cellular and molecular mechanisms involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer´s and Parkinson’s diseases. In this way, novel journeys for the development of new pharmacological strategies more effective for the treatment of neurodegenerative diseases may be initiated.Show more >
Syringomyelia in combination with inherent or acquired hindbrain abnormalities is the non seldom and at the same time controversial issue.
Purpose: The etiology and pathogenesis creates a lot of discussion.
Methods: Experimental syringomyelia was ind... uced in 20 anesthetized rabbits by injecting 0.5 ml of 25% kaolin suspension into the cisterna magna. Six rabbits with puncture and injection sterile saline NaCl were used as a control. The animals were sacrificed 1, 2, 4 and 6 months after the kaolin injection. Four hydrocephalus rabbits were sacrificed in 17 hours after the puncture of lateral ventricle with injection of solution of colloidal gold labeled human albuminum. The sections of the brain and spinal cord were stained with hematoxylin and eosin by Nissle and Marchi methods and with immunogold technique. Retropharyngeal lymph nodes of the animals were examined by electron microscopy.
Conclusion: Our observation showed that water hammer effect and internal destruction of the spinal cord may lead to continuous antigen stimulation of regional lymph nodes and play an important role in pathogenesis of experimental syringomyelia.Show more >
The infectivity and pathogenesis: SARS-CoV-2, the causative agent of Covid-19, involves Angiotensin-converting enzyme 2 (ACE2) receptors on type II alveolar type 2 (AT2) cells in lungs. Apart from, the upper and lower respiratory tracts, the disease ... affects the gastrointestinal system prominently, as evidenced by the significant GI symptoms, early in the course of the disease. In addition, the virus infects ACE2-bearing cells in other organs including the heart and blood vessels, brain, and kidneys.
Clinical features and morbidity: The clinical spectrum of COVID-19 varies from asymptomatic or pauci-symptomatic presentation to moderate to severe states characterized by respiratory failure necessitating mechanical ventilation and ICU support and those manifesting critical clinical condition with complications like sepsis, septic shock, and multiple organ dysfunction failure. The CT chest is an important tool for early identification of COVID-19 pneumonia as well as for prognostic purposes.
The recovery and residual damage: The recovery and other outcomes vary depending on age and other aspects including sex, comorbidities, and genetic factors. The outlook for older adults, who account for a disproportionate share of critical disease, is unfavorable, and most of those who survive are unlikely to return to their previous level of functioning. The disease affects their long-term health and quality of life as well as brings in propensity for truncated post-disease survival.
COVID-19 aftermath and follow up: The patients discharged from hospital following severe COVID-19, continue to suffer with lingering impact of the disease as well as that of the emergency treatments that saved their life. The post-infection reduced exercise tolerance and other subtle factors, like post viral fatigue syndrome, post-traumatic stress disorder, impaired concentration, delirium, and disturbed sleep-wake cycle often underly the functional impairment. In fact, there is need of step-down care and later a multidisciplinary support involving regular clinical assessment, respiratory review, physiotherapy, nutritional advice, and psychiatric support.
Conclusion: The life after COVID-19: After recovery from the disease, the virus SARS-CoV-2, may persist for uncertain period. In addition, the chance of reinfection cannot be ruled out. The vitamin D supplementation may be helpful. In general, the quality of life (QOL) in ICU survivors improves but remains lower than general population levels, but most of the patients adapt well to their level of self-sufficiency and QOL. Also, the debility due to co-morbidities may further compromise the activity of daily living and QOL issues. The Age and severity of illness appear to be the major predictors of post-discharge physical functioning.Show more >
In late 2019, a pandemic crisis started in Wuhan, China, swept the whole world. The disease is caused by the SARS-CoV-19 virus that belongs to the corona family of viruses. The virus mainly caused failure of respiration, and led to many deaths worldw... ide. The main focus of research and medicine is to find more about the virus, as well as the development of effective preventive and therapeutic measures. While many trials and opinions have been published, which might support or contradict each other, this article tries to provide a simplified viewpoint about the disease. We highly recommend the therapeutic strategies to include drug combinations that can target the pathogenesis at many levels. For example, a combination of an effective anti-viral Remdesivir, soulable ACE2, and an immune modulator.Show more >
Introduction: SARS-CoV-2 life cycle: The disease which reportedly began in Chinese city Wuhan in November-December 2019 manifesting as severe respiratory illness, soon spread to various parts of the world, and was named COVID-19, and declared a pande... mic by WHO. The life cycle of SARS-CoV-2 begins with membrane fusion mediated by Spike (S) protein binding to the ACE2 receptors. Following viral entry and release of genome into the host cell cytoplasm there occurs replication and transcription to generate viral structural and non-structural proteins. Finally, VLPs are produced and the mature virions are released from the host cell.
Immunogenicity of the spike protein: The S protein is considered the main antigenic component among structural proteins of SARS-CoV-2 and responsible for inducing the host immune response. The neutralising antibodies (nAbs) targeting the S protein are produced and may confer a protective immunity against the viral infection. Further, the role of the S protein in infectivity also makes it an important tool for diagnostic antigen-based testing and vaccine development. The S-specific antibodies, memory B and circulating TFH cells are consistently elicited following SARS-CoV-2 infection, and COVID-19 vaccine shots in clinical trials.
The emerging SARS-CoV-2 variants: The early genomic variations in SARS-CoV-2 have gone almost unnoticed having lacked an impact on disease transmission or its clinical course. Some of the recently discovered mutations, however, have impact on transmissibility, infectivity, or immune response. One such mutation is the D614G variant, which has increased in prevalence to currently become the dominant variant world-over. Another, relatively new variant, named VUI-202012/01 or B.1.1.7 has acquired 17 genomic alterations and carries the risk of enhanced infectivity. Further, its potential impact on vaccine efficacy is a worrisome issue.
Conclusion: THE UNMET CHALLENGES: COVID-19 as a disease and SARS-CoV-2 as its causative organism, continue to remain an enigma. While we continue to explore the agent factors, disease transmission dynamics, pathogenesis and clinical spectrum of the disease, and therapeutic modalities, the grievous nature of the disease has led to emergency authorizations for COVID-19 vaccines in various countries. Further, the virus may continue to persist and afflict for years to come, as future course of the disease is linked to certain unknown factors like effects of seasonality on virus transmission and unpredictable nature of immune response to the disease.Show more >
Introduction: Lipoprotein (a) [Lp(a)] is a marker for cardiovascular disease, involved in pathogenesis and progression of atherosclerosis. In selected high-risk patients, lipoprotein-apheresis could optimize secondary prevention and improve prognosis... .
Aim: We presented the case of a 49-year-old man with high lipoprotein (a) levels and recurrent cardiac adverse events, despite maximal pharmacological therapy.
Case report: Four years before the admission at our Centre, he presented an anterior STEMI, treated with angioplasty and implantation of a drug eluting stent on left anterior descending artery, at the age of 47 years, in September 2012; one month later, the patients presented a new episode of angina, and exams showed a critical stenosis in the right coronary artery, treated by angioplasty and implantation of drug eluting stent. Because of high Lp(a) plasma levels, patient was subsequently on regularly 7-10 day lipoprotein apheresis.
Results and discussion: A thrombophilic screening was performed, showing the simultaneous presence of heterozygous V Leiden mutation and prothrombin G20210A mutation. He referred to our Centre in order to optimize therapy; we performed an endothelial function assessment showing a severe dysfunctional pattern.
Because of these findings, we prescribed dual antiplatelet therapy, and we added omega-3 fatty acids and association with nicotinic acid/laropiprant. According with current guidelines, considering the high risk of bleeding, we preferred not to administer anticoagulant therapy. At 6-month and 1-year follow up the patient continued lipoprotein apheresis and was asymptomatic for other cardiovascular events.
Conclusions: The assessment for the eventual presence of thrombophilia might become a useful tool in clinical practice for high-risk selected patients.Show more >
Linear IgA bullous dermatosis (LABD) is a rare, chronic, autoimmune bullous dermatosis affecting young children and adults. The exact pathogenesis of this disease is still unknown, although both humoral and cellular immune response are involved. Clin... ically, it may show heterogeneous skin manifestations. However, it is characterized histologically by linear immunoglobulin A (IgA) deposits over the basal membrane, causing subepidermal blisters. Studies on LABD are relatively sparse and most of the publications are small series or single case reports. Several treatments are reported in literature, however, they should be used with care due to the risk of side effects. We report a case of linear IgA dermatosis with generalized lesions in a 7 year old child, with good outcome under dermocorticoids and antibiotics.Show more >
Background: The plant Artemisia annua has been used in traditional Chinese medicine for many years. Rich in bioactive molecules, the A. annua plant is used to extract the anti-malaria compound artemisinin (< 1%), which results in most of the plant... being unutilized. One byproduct of artemisinin extraction is artemisia naphtha (AN), which has yet to be studied extensively.
Aims: Study the activity of a novel AN oil extract against microbes, pro-inflammatory cytokines, and dermatological endpoints that are key for eczema and acne pathogenesis to determine if an effective A. annua extract for these skin conditions can be developed.
Methods: Gas chromatography-mass spectrometry was performed to determine the composition of AN oil. P. acnes, S. aureus, M. furfur, and C. albicans were cultured to determine minimal inhibitory concentration. in vitro studies utilizing keratinocytes and macrophages were treated with AN oil and gene expression measured by quantitative RT-PCR. A 13-subject clinical trial was performed with 1% AN oil Gel to assess its potential benefits for sensitive and acne prone skin.
Results: AN oil upregulates filaggrin gene expression and possesses antimicrobial and anti-inflammatory activity inhibiting LPS, S. aureus and "Th2 induced" pro-inflammatory mediator release (IL-6, IL-8 and TSLP). Clinical assessment of 1% AN Gel shows it reduces acne blemishes and the appearance of redness.
Conclusion: Previously an underutilized and unpurified byproduct, AN is now the source to develop the first topical AN oil for cosmetic use with an activity profile that suggests it is effective for those with sensitive and/or acne prone skin.Show more >
Starting from observation of pathogenesis of KURU disease we try to investigate the immunologic role played by central nervous systems. A deeply knowledge in the transmission model of this pathology can be an imaging/diagnostic tool to Verify the pro... gression of this prion molecule from gastro intestinal systems to the brain. (After cannibalistic behavior). The prions can be considered a sort of trace ant in KURU to monitoring this process and immune- brain relationship. Interesting information can be obtained useful to produce new pharmacological strategies in some other degenerative brain disease involving innate immune system activation.Show more >
Broad medleys of research have recognized the microglial activation in perilous psychiatric maladies such as schizophrenia, bipolar disorder, and major depressive disorder. There is a scenario of enlivening of peripheral monocytic cells along with th... e microglial interactions within the body while considering the Pathogenesis of psychiatric disorders. this review, epitomize and discuss the activation of microglia and monocytic cells in psychiatric disorders, thereby showcasing the potential association between these cell types and the Pathogenisis of the ailment , and proffer perspectives for future research on these processes.Show more >
Background: Drosophila models of amyotrophic lateral sclerosis (ALS) have been widely used in understanding molecular mechanisms of ALS pathogenesis as well as discovering potential targets for therapeutic drugs. Mutations in the copper/zinc superoxi... de dismutase (SOD1) cause ALS by gain of toxic functions and induce toxicity in fly motor neurons.
Results: In this study, we have determined that human carbonic anhydrase I (CA1) can alleviate mutant SOD1-induced motor neuron toxicity in the transgenic fly model of ALS. Interestingly, we found that motor neuron expression of CA1 could independently induce locomotion defect as well as decreasing the survival rate. In addition, CA1-induced toxicity in motor neurons is anhydrase activity-dependent. Mechanistically, we identified that both SOD1- and CA1-induced toxicity involve the activation of eIF2α in the ER stress response pathway. Downstream activation of the JNK pathway has also been implicated in the induced toxicity.
Conclusion: Our results have confirmed that SOD1-induced toxicity in fly motor neuron also involves endoplasmic reticulum (ER) stress pathway. More importantly, we have discovered a new cellular role that CA1 plays by antagonizing mutant SOD1-induced toxicity in motor neurons involving the ER stress pathway. Such information can be potentially useful for further understanding disease mechanisms and developing therapeutic targets for ALS. Show more >
The biological changes caused by oxidative stress (OS) are known to be involved in the etiology of neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. The brain is ... particularly vulnerable to OS due to its high lipid content and extensive consumption of oxygen. OS processes, particularly the excessive production of reactive oxygen species (ROS), play a critical role in how neurodegenerative disorders develop. This is evidenced by in vivo studies investigating various biomolecules related to OS, such as products of lipid and DNA oxidation. Accordingly, ROS can also cause oxidative-related damage in neurodegenerative disorders, including dopamine auto-oxidation, mitochondrial dysfunction, glial cell activation, α-synuclein aggregation, excessive free iron, and changes in calcium signaling. Furthermore, excessive levels of cellular oxidants reduce antioxidant defenses, which in turn propagate the cycle of OS. As such, it is increasingly important to determine the linkage between a high intake of antioxidants through dietary interventions and a lower risk of developing neurodegenerative diseases. Indeed, in addition to modulating the immune system, optimal nutritional status is capable of changing various processes of neuroinflammation known to be involved in the pathogenesis of neurodegeneration. Accordingly, a better understanding of the role ROS plays in the etiology of neurodegeneration is needed, along with the identification of dietary interventions that may lead to improved therapeutic strategies for both the treatment and prevention of neurodegenerative disorders. Therefore, this review presents a comprehensive summary of the role of ROS in the pathogenesis of neurodegenerative disorders. In addition, nutrients believed to be useful for mitigating and counteracting ROS are discussed. Show more >
Background: A misguided auto-reactive injury is responsible for several types of central nervous system (CNS) conditions in pediatrics. We propose that, in some of these conditions, the adaptive immune system has a common cellular immune pathogenesis... , driven predominantly by T cells, despite variability on the phenotypical clinical presentation.
Methods: We have characterized the CD4+/CD8+ adaptive immune response (AIR) on pediatric patients presenting with clinical symptoms compatible with Neuroimmune Disorders (NID). Flow cytometry with deep immunophenotyping of T cells was performed on peripheral blood obtained during the acute clinical phase and compared to an age-matched cohort group (Co).
Results: We found that pediatric patients with confirmed NID, exhibit a pattern of dysregulation of CD4+ lineages associated with autoimmune processes.
Discussion: The autoimmune associated CD4+ dysregulation was associated with patients with NID, as compared to healthy controls and patients with non-autoimmune diagnoses. If we can improve our capacity for early accurate diagnosis and meaningful disease monitoring of pathogenic T cell subsets, we can both expedite disease detection and may serve as a guide to the administration of effective immunotherapeutic agents.Show more >
Huntington’s disease (HD) is an incurable neurodegenerative disease that causes involuntary movements, emotional lability, and cognitive dysfunction. HD symptoms usually develop between ages 30 and 50, but can appear as early as 2 or as late as 80 ye... ars. Currently no neuroprotective and neurorestorative interventions are available. Early multimodal intervention in HD is only possible if the genetic diagnosis is made early. Early intervention in HD is only possible if genetic diagnosis is made at the disease onset or when mild symptoms manifest. Growing evidence and understanding of HD pathomechanism has led researchers to new therapeutic targets. Here, in this article we will talk about the multimodal treatment strategies and recent advances made in this field which can be used to target the HD pathogenesis at its most proximal level.Show more >
Non-alcoholic fatty liver disease (NAFLD) is a condition that is associated with cirrhosis and hepatocellular carcinoma, and is increasing in prevalence worldwide. Sleep disruptions are commonly seen in NAFLD, and the disease process is associated wi... th sleep disorders, including obstructive sleep apnea, circadian rhythm disorders, and insufficient sleep. The intermittent hypoxia seen in obstructive sleep apnea may contribute to fibrotic changes in the liver.A major component of this linkage may be related to gut microbiome changes. One notable change is increase in Bacteroidetes/Firmicutes ratio, and decrease in flora that ferment fiber into anti-inflammatory short-chain fatty acids. Several therapeutic options exist for NAFLD that target both sleep and NAFLD, including non-pharmacological factors, such as lifestyle modification (mainly diet and exercise). Pharmacological options include melatonin, Vitamin E, thiazolidinediones, and fecal microbiota transplantation.Core tipThe pathogenesis of non-alcoholic fatty liver disease is closely tied to sleep and circadian rhythm abnormalities, through shared inflammatory pathways and altered metabolism. This review explores the pathogenesis of NAFLD in the context of sleep and circadian abnormalities. The associated inflammatory response is linked to changes in gut-microbiome interactions that contribute to the disease process. Understanding of this linkage has implications for various therapies for disease mitigation.Show more >
Background: Varied clinical manifestations, complex pathogenesis, and different viral serotypes make it difficult to predict the course of dengue disease. Many studies have been conducted on the prognostic factors for the occurrence of dengue shock s... yndrome (SSD), but all use the 2017 World Health Organization (WHO) guidelines. Aim: This study aims to determine the prognostic factors for the occurrence of SSD based on WHO guidelines in 2011. Method: Retrospective study using medical record data of pediatric patients aged 0 to <18 years with a diagnosis of dengue fever dengue (DHF), SSD, and expanded dengue syndrome (EDS) that meet WHO criteria in 2011 at the reputable database from 2017 to December 2020. Independent variables, namely gender, age, nutritional status, secondary dengue infection, leukopenia, abdominal pain, gastrointestinal bleeding, hepatomegaly, and plasma leakage. Shock is the dependent variable. Multivariate analysis using logistic regression analysis. Results: Subjects who met the study criteria were 145 patients, 52 (35.8%) of whom had SSD. Five of 52 SSD patients went into shock during hospitalization. The bivariate analysis yielded significant factors including, malnutrition, overnutrition and obesity, gastrointestinal bleeding, hemoconcentration, ascites, leukocytes 5,000 mm 3, encephalopathy, enzyme elevation heart, and overload. The results of multivariate analysis showed that hemoconcentration variables and elevated liver enzymes were factors of SSD Prognosis. Conclusion: Hemoconcentration and elevated liver enzymes are prognostic factors for SSD. Show more >
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