Hanan Hassan Fouad

Irreversible myocardial injury causes the exhaustion of cellular adenosine triphosphate (ATP) contributing to heart failure (HF). Cyclocreatine phosphate (CCrP) was shown to preserve myocardial ATP during ischemia and maintain cardiac function in various animal models of ischemia/reperfusion. We tested whether CCrP administered prophylactically/therapeutically prevents HF secondary to ischemic injury in an isoproterenol (ISO) rat model. Thirty-nine rats were allocated into five groups: control/saline, control/CCrP, ISO/saline (85 and 170 mg/kg/day s.c. for 2 consecutive days), and ISO/CCrP (0.8 g/kg/day i.p.) either administrated 24 h or 1 h before ISO administration (prophylactic regimen) or 1 h after the last ISO injection (therapeutic regimen) and then daily for 2 weeks. CCrP protected against ISO-induced CK-MB elevation and ECG/ST changes when administered prophylactically or therapeutically. CCrP administered prophylactically decreased heart weight, hs-TnI, TNF-α, TGF-β, and caspase-3, as well as increased EF%, eNOS, and connexin-43, and maintained physical activity. Histology indicated a marked decrease in cardiac remodeling (fibrin and collagen deposition) in the ISO/CCrP rats. Similarly, therapeutically administered CCrP showed normal EF% and physical activity, as well as normal serum levels of hs-TnI and BNP. In conclusion, the bioenergetic/anti-inflammatory CCrP is a promising safe drug against myocardial ischemic sequelae, including HF, promoting its clinical application to salvage poorly functioning hearts.

Irreversible myocardial injury causes the exhaustion of cellular adenosine triphosphate (ATP) contributing to heart failure (HF). Cyclocreatine phosphate (CCrP) was shown to preserve myocardial ATP during ischemia and maintain cardiac function in various animal models of ischemia/reperfusion. We tested whether CCrP administered prophylactically/therapeutically prevents HF secondary to ischemic injury in an isoproterenol (ISO) rat model. Thirty-nine rats were allocated into five groups: control/saline, control/CCrP, ISO/saline (85 and 170 mg/kg/day s.c. for 2 consecutive days), and ISO/CCrP (0.8 g/kg/day i.p.) either administrated 24 h or 1 h before ISO administration (prophylactic regimen) or 1 h after the last ISO injection (therapeutic regimen) and then daily for 2 weeks. CCrP protected against ISO-induced CK-MB elevation and ECG/ST changes when administered prophylactically or therapeutically. CCrP administered prophylactically decreased heart weight, hs-TnI, TNF-α, TGF-β, and caspase-3, as well as increased EF%, eNOS, and connexin-43, and maintained physical activity. Histology indicated a marked decrease in cardiac remodeling (fibrin and collagen deposition) in the ISO/CCrP rats. Similarly, therapeutically administered CCrP showed normal EF% and physical activity, as well as normal serum levels of hs-TnI and BNP. In conclusion, the bioenergetic/anti-inflammatory CCrP is a promising safe drug against myocardial ischemic sequelae, including HF, promoting its clinical application to salvage poorly functioning hearts.

BACKGROUND: Graft-versus-host disease (GVHD) is one of the most severe complications in patients with acute myeloid leukemia (AML) who underwent allogenic hematopoietic stem cell transplantation (HSCT). This study addressed the effectiveness and safety outcomes of high dose post-transplant cyclophosphamide (PT-CY) followed by cyclosporine A (CSA) as a GVHD prophylaxis protocol.

PATIENTS AND METHODS: From January 2019 to March 2021, AML patients who underwent HSCT, and received high-dose PT-CY followed by CSA were prospectively recruited, assessed, and followed up for one-year post-transplantation (PT). The cumulative incidences of both acute GVHD (aGVHD) at 100 days PT, and chronic GVHD (cGVHD) at one-year PT were assessed.

RESULTS: This study included 52 patients. The cumulative incidence (95% CIs) of aGVHD was 2.3% (0.3 - 15.4%), while the cumulative incidence of cGVHD was 23.2% (12.2-41.5%). The cumulative incidence of relapse and non-relapse mortality were 15.6%, and 7.9%, respectively. The median duration to reach neutrophil and platelet engraftment was 17 and 13 days, respectively. The overall, progression-free, and GVHD-free/relapse-free survival rates (95% CIs) were 89.6% (76.6 - 95.6%), 77.7% (62.1-87.5%), and 58.2% (41.6 - 71.7%) respectively. The cumulative incidences of the main transplant-related complications were; neutropenic sepsis (48.3%), cytomegalovirus reactivation (21.7%), pneumonia (13.8%), hemorrhagic cystitis (17.8%), septic shock (4.9%), and CSA toxicity (48.9%).

CONCLUSION: PT-CY followed by CSA was associated with low cumulative incidences of both aGVHD and cGVHD without increase in either the relapse or transplant-related complications; so, considered as a promising protocol to be widely applied in the settings of HLA-matched donors.

INTRODUCTION: The terminal ventricle, also known as the fifth ventricle, is a tiny relic cavity in the conus medullaris of the human spinal cord. Our purpose in bringing attention to this condition is to get the word out about the signs and symptoms, diagnostic hurdles, and therapeutic options available for it.

METHODS: All relevant studies involving patients diagnosed with ventriculus terminalis (VT) were retrieved from PubMed, Google Scholar, and Scopus. Studies published in complete English language reports were included. The terms VT, terminal ventricle, and 5 ventricle. Age, gender, presenting symptoms, magnetic resonance imaging findings, treatment, and outcome of patients with ventriculus terminalis were all included and recorded.

RESULTS: The average age of the patients was 39 years, and there were 13 men among them (14.4%). Motor deficits and sciatica were the most commonly reported symptoms in 38 and 34 patients (42.2%, 37.7%), respectively. In 48 patients (53.3%), cyst fenestration was performed, and in 25 patients (27.7%), myelotomy was performed. Fifty-eight patients (64.4%) saw a reduction in cyst size after surgery. The majority of patients reported an improvement in their symptoms in 64 cases (51.1%), with only three cases (3.3%) reporting a worsening.

CONCLUSIONS: In cases where the VT is the source of symptoms such as motor, sensory, or bladder dysfunction, surgical intervention is recommended. This review compiles information from the available literature to shed light on the anatomy, clinical presentation, imaging, and treatment options for this variant. It also aims to pinpoint any potential drawbacks or restrictions connected to the surgical techniques.

INTRODUCTION: The terminal ventricle, also known as the fifth ventricle, is a tiny relic cavity in the conus medullaris of the human spinal cord. Our purpose in bringing attention to this condition is to get the word out about the signs and symptoms, diagnostic hurdles, and therapeutic options available for it.

METHODS: All relevant studies involving patients diagnosed with ventriculus terminalis (VT) were retrieved from PubMed, Google Scholar, and Scopus. Studies published in complete English language reports were included. The terms VT, terminal ventricle, and 5 ventricle. Age, gender, presenting symptoms, magnetic resonance imaging findings, treatment, and outcome of patients with ventriculus terminalis were all included and recorded.

RESULTS: The average age of the patients was 39 years, and there were 13 men among them (14.4%). Motor deficits and sciatica were the most commonly reported symptoms in 38 and 34 patients (42.2%, 37.7%), respectively. In 48 patients (53.3%), cyst fenestration was performed, and in 25 patients (27.7%), myelotomy was performed. Fifty-eight patients (64.4%) saw a reduction in cyst size after surgery. The majority of patients reported an improvement in their symptoms in 64 cases (51.1%), with only three cases (3.3%) reporting a worsening.

CONCLUSIONS: In cases where the VT is the source of symptoms such as motor, sensory, or bladder dysfunction, surgical intervention is recommended. This review compiles information from the available literature to shed light on the anatomy, clinical presentation, imaging, and treatment options for this variant. It also aims to pinpoint any potential drawbacks or restrictions connected to the surgical techniques.

INTRODUCTION: The terminal ventricle, also known as the fifth ventricle, is a tiny relic cavity in the conus medullaris of the human spinal cord. Our purpose in bringing attention to this condition is to get the word out about the signs and symptoms, diagnostic hurdles, and therapeutic options available for it.

METHODS: All relevant studies involving patients diagnosed with ventriculus terminalis (VT) were retrieved from PubMed, Google Scholar, and Scopus. Studies published in complete English language reports were included. The terms VT, terminal ventricle, and 5 ventricle. Age, gender, presenting symptoms, magnetic resonance imaging findings, treatment, and outcome of patients with ventriculus terminalis were all included and recorded.

RESULTS: The average age of the patients was 39 years, and there were 13 men among them (14.4%). Motor deficits and sciatica were the most commonly reported symptoms in 38 and 34 patients (42.2%, 37.7%), respectively. In 48 patients (53.3%), cyst fenestration was performed, and in 25 patients (27.7%), myelotomy was performed. Fifty-eight patients (64.4%) saw a reduction in cyst size after surgery. The majority of patients reported an improvement in their symptoms in 64 cases (51.1%), with only three cases (3.3%) reporting a worsening.

CONCLUSIONS: In cases where the VT is the source of symptoms such as motor, sensory, or bladder dysfunction, surgical intervention is recommended. This review compiles information from the available literature to shed light on the anatomy, clinical presentation, imaging, and treatment options for this variant. It also aims to pinpoint any potential drawbacks or restrictions connected to the surgical techniques.

INTRODUCTION: The terminal ventricle, also known as the fifth ventricle, is a tiny relic cavity in the conus medullaris of the human spinal cord. Our purpose in bringing attention to this condition is to get the word out about the signs and symptoms, diagnostic hurdles, and therapeutic options available for it.

METHODS: All relevant studies involving patients diagnosed with ventriculus terminalis (VT) were retrieved from PubMed, Google Scholar, and Scopus. Studies published in complete English language reports were included. The terms VT, terminal ventricle, and 5 ventricle. Age, gender, presenting symptoms, magnetic resonance imaging findings, treatment, and outcome of patients with ventriculus terminalis were all included and recorded.

RESULTS: The average age of the patients was 39 years, and there were 13 men among them (14.4%). Motor deficits and sciatica were the most commonly reported symptoms in 38 and 34 patients (42.2%, 37.7%), respectively. In 48 patients (53.3%), cyst fenestration was performed, and in 25 patients (27.7%), myelotomy was performed. Fifty-eight patients (64.4%) saw a reduction in cyst size after surgery. The majority of patients reported an improvement in their symptoms in 64 cases (51.1%), with only three cases (3.3%) reporting a worsening.

CONCLUSIONS: In cases where the VT is the source of symptoms such as motor, sensory, or bladder dysfunction, surgical intervention is recommended. This review compiles information from the available literature to shed light on the anatomy, clinical presentation, imaging, and treatment options for this variant. It also aims to pinpoint any potential drawbacks or restrictions connected to the surgical techniques.

INTRODUCTION: Globally, it is estimated that 290,000 patients infected with hepatitis C virus (HCV) died from hepatitis C consequences, including cirrhosis and hepatocellular carcinoma in 2019. Although daclatasvir (DCV), combined with sofosbuvir (SOF), is effective in HCV patients, the new pan-genotypic combinations are considered by many as more cost-effective and successful in eradicating HCV infection.

AREAS COVERED: This review discusses the safety, efficacy, and cost-effectiveness of DCV as an HCV treatment option based on real-world studies and pharmacoeconomic evaluations.

EXPERT OPINION: Real-life studies suggest that SOF/DCV has acceptable sustained virological response and can be used successfully to manage HCV. Nonetheless, the use of SOF/DCV is limited by the longer treatment duration in genotype (GT)-3 patients and the need for ribavirin (RBV) in treatment-experienced patients which increases the likelihood of adverse effects. DCV is likely to remain as a therapeutic option for the management of GT-1, GT-2, and GT-4 patients in resource limited settings, while GT-3 patients are more likely to benefit from RBV-free direct-acting antiviral combinations such as SOF/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks. The introduction of generics for these new pan-genotypic drugs would likely eliminate the need for SOF/DCV in the near future.

BACKGROUND: However, disturbances in cellular energy demarcate neuronal hyperexcitability in essential tremor (ET); nevertheless, no available data relates energy sensors and GABAergic neurotransmission in ET. Noteworthy, reports have asserted dapagliflozin's (DAPA) role in enhancing autophagic sensors in other disorders. Herein, this study aims to investigate DAPA's impact on the GABA receptor subunit (GABA R2), notwithstanding the GABA A involvement, in an ET model.

METHODS: ET was induced by a single dose of harmaline (30 mg/kg; i.p.), while DAPA (1 mg/kg/day; p.o.) was given for 5 days before ET induction. The autophagic sensors were examined by injecting a single dose of dorsomorphin (DORSO) AMPK inhibitor (0.2 mg/kg; i.p.) on the 5 day before ET induction.

RESULTS: DAPA decreased the HAR-induced tremor score and alleviated motor disabilities observed in the open field, rotarod, wire grip strength, and gait kinematics confirmed by reduced electrical activity in electroencephalogram. In the cerebella, DAPA curbed HAR-evoked inflammatory cytokines, apoptotic markers, and glutamate while restoring the disturbed GABA, BDNF, LKB1, p-AMPK, and GABA R2 levels. DAPA's effect was mostly obliterated by DORSO.

CONCLUSION: DAPA offers a potential neuroprotective effect in ET by augmenting the neuronal inhibitory machinery via suppressing the inflammatory and excitotoxicity systems through LKB1/p-AMPK/GABA R2 signaling.

BACKGROUND: However, disturbances in cellular energy demarcate neuronal hyperexcitability in essential tremor (ET); nevertheless, no available data relates energy sensors and GABAergic neurotransmission in ET. Noteworthy, reports have asserted dapagliflozin's (DAPA) role in enhancing autophagic sensors in other disorders. Herein, this study aims to investigate DAPA's impact on the GABA receptor subunit (GABA R2), notwithstanding the GABA A involvement, in an ET model.

METHODS: ET was induced by a single dose of harmaline (30 mg/kg; i.p.), while DAPA (1 mg/kg/day; p.o.) was given for 5 days before ET induction. The autophagic sensors were examined by injecting a single dose of dorsomorphin (DORSO) AMPK inhibitor (0.2 mg/kg; i.p.) on the 5 day before ET induction.

RESULTS: DAPA decreased the HAR-induced tremor score and alleviated motor disabilities observed in the open field, rotarod, wire grip strength, and gait kinematics confirmed by reduced electrical activity in electroencephalogram. In the cerebella, DAPA curbed HAR-evoked inflammatory cytokines, apoptotic markers, and glutamate while restoring the disturbed GABA, BDNF, LKB1, p-AMPK, and GABA R2 levels. DAPA's effect was mostly obliterated by DORSO.

CONCLUSION: DAPA offers a potential neuroprotective effect in ET by augmenting the neuronal inhibitory machinery via suppressing the inflammatory and excitotoxicity systems through LKB1/p-AMPK/GABA R2 signaling.

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The current study is regarding the development and characterization of Darifenacin-loaded self-assembled liquid crystal cubic nanoparticles (LCCN). An anhydrous approach was used for the preparation of these cubic nanoparticles using a hydrotropic agent (propylene glycol), with minimal energy input. Upon dispersion in aqueous medium, the system was successfully transformed to cubosomal nanoparticles counterpart as depicted by transmission electron micrographs. A Box-Behnken design was used to optimize formulation variables, namely A: amount of GMO, B: amount of Pluronic F127, C: amount of PG, and D: amount of HPMC. The design has generated 29 formulae which were tested regarding drug content uniformity, dispersibility in water, particle size, zeta potential, polydispersity index, and in vitro release behavior. The numerical optimization algorithms have generated an optimized formula with high desirability ≈ 1. The optimized formula displayed small particle size, good homogeneity, and zeta potential along with controlled in vitro release profile and ex vivo permeation through rabbit intestine. Thus, self-assembled LCCN might offer an alternative anhydrous approach for the preparation of cubosomal nanoparticles with controlled release profile for a possibly better control of overactive bladder syndrome which tremendously affect the overall life quality.