Long-term atorvastatin treatment decreases heart maximal oxygen consumption and its vulnerability to in vitro oxidative stress in Watanabe heritable hyperlipidemic rabbit.

Statins are currently used in prevention of cardiovascular diseases in high-risk populations, and could be considered in primary prevention. However, few studies are available on the long-term effects of low doses of statins, especially on mitochondrial function and reactive oxygen species (ROS) metabolism at cardiac level. This study aimed to determine potential effects of a long-term atorvastatin treatment, at low-dose concentration, on the myocardium mitochondrial respiration. Thirty-four Watanabe rabbits were treated or not with atorvastatin (2.5 mg·kg-1·day-1) from the age of 3 to 12 months. Every 3 months, proton leak, basal (V0), and maximal (Vmax) mitochondrial respiration on cardiac permeabilized fibers were measured. Additionally, the vulnerability to ROS, cardiac enzymatic antioxidant defenses, and oxidative damage (lipoperoxidation) were analyzed. Proton leak increased over the duration of the experiment (up to 60% from Vmax at 12 months). Moreover, the statin treatment induced a decrease of Vmax and a decrease of ROS susceptibility of cardiac mitochondria. However, the lipoperoxidation and the antioxidant defenses were not dependent on the presence of statin treatment, or on its duration. This is the first study showing a protective effect of long-term statins treatment against the ROS susceptibility in the cardiac muscle.

Venous sinus stenting under conscious sedation.

BACKGROUND: Venous sinus stenting (VSS) is an increasingly performed procedure for the treatment of idiopathic intracranial hypertension (IIH) refractory to medical treatment. VSS is typically performed under general anesthesia. OBJECTIVE: To present our experience of VSS in patients with IIH performed under conscious sedation. METHODS: Retrospective review of a prospectively maintained database of all patients with IIH who underwent VSS in a single center between September 2019 and January 2024. The sedation protocol consisted of a remifentanil-based target-controlled infusion. Patients' clinical and radiological data, dosage of anesthesia, procedural characteristics, and outcomes were collected. RESULTS: Twenty-six patients with IIH underwent venous manometry (VM) and VSS under awake sedation and were included in our study. Patients were predominantly women (24/26) with a median age (IQR) of 33 (13) years. The median (IQR) body mass index was 34 (10) kg/m2. There was no need for general anesthesia conversion. Technical success was achieved in all patients. Median (IQR) follow-up after stenting was 7 (2) months. All patients reported resolution of the pulsatile tinnitus; headaches regressed in 20/24 (83.3%) patients and papilledema improved in 16/20 (80%). Only one non-neurological complication (retroperitoneal hematoma) occurred, without any permanent morbidity or mortality. CONCLUSION: Our study confirms that performing VM and VSS under conscious sedation is safe and feasible. Conscious sedation is a viable alternative to general anesthesia for managing IIH in these patients.

Noncardiac Lebanese hospitalized adult patients' awareness of their coronary artery disease risk factors.

BACKGROUND: Noncommunicable diseases are the leading cause of death in Lebanon, with cardiovascular diseases accounting for almost half of the annual deaths. PURPOSE: We aimed to determine awareness of noncardiac Lebanese hospitalized patients for their coronary artery disease risk factors, their level of adherence to medications or lifestyle modifications, and assess factors associated with awareness. MATERIALS AND METHODS: A cross-sectional study was conducted in 14 hospitals with a total of 382 patients. Levels of awareness were evaluated by the comparison of self-report with measurements and laboratory test results. Healthy behaviors and adherence to treatment were evaluated. Factors associated with better awareness were studied using multivariate regressions, while adherence to treatments and healthy lifestyle were described for the different risk factors and in the Framingham Risk Score categories. RESULTS: Our work revealed a moderate-to-high level of awareness (58.7% for overweight/obesity, 75% for hypertension, 85.7% for diabetes, and 86.4% for dyslipidemia) among patients for most cardiovascular risk factors, but a low-to-moderate level of adherence for some interventions such as physical exercise, weight loss, and smoking cessation. CONCLUSION: The results emphasize on the importance of educational campaigns on healthy habits and screening to improve early diagnosis, increase patients' awareness of their risk factors, and, therefore, optimize primary prevention.

Biomaterials in Tendon and Skeletal Muscle Tissue Engineering: Current Trends and Challenges.

Tissue engineering is a promising approach to repair tendon and muscle when natural healing fails. Biohybrid constructs obtained after cells’ seeding and culture in dedicated scaffolds have indeed been considered as relevant tools for mimicking native tissue, leading to a better integration in vivo. They can also be employed to perform advanced in vitro studies to model the cell differentiation or regeneration processes. In this review, we report and analyze the different solutions proposed in literature, for the reconstruction of tendon, muscle, and the myotendinous junction. They classically rely on the three pillars of tissue engineering, i.e., cells, biomaterials and environment (both chemical and physical stimuli). We have chosen to present biomimetic or bioinspired strategies based on understanding of the native tissue structure/functions/properties of the tissue of interest. For each tissue, we sorted the relevant publications according to an increasing degree of complexity in the materials’ shape or manufacture. We present their biological and mechanical performances, observed in vitro and in vivo when available. Although there is no consensus for a gold standard technique to reconstruct these musculo-skeletal tissues, the reader can find different ways to progress in the field and to understand the recent history in the choice of materials, from collagen to polymer-based matrices.

A Rare Case of a Ruptured Metastatic Hepatic Lesion from a Jejunal Gastrointestinal Stromal Tumor (GIST) Treated by Arterial Embolization.

BACKGROUND Gastrointestinal stromal tumors (GISTs) are rare gastrointestinal neoplasms. The spontaneous rupture of a jejunal GIST is very rare and spontaneous rupture of liver metastasis from an intestinal GIST is even rarer with only a few cases reported in the literature. CASE REPORT In this article, we reported a case of spontaneous rupture of a liver metastasis from a malignant jejunal GIST that presented with active tumoral bleeding, hypovolemic shock, and hemoperitoneum. The patient was successfully treated with arterial embolization of the tumor. CONCLUSIONS In appropriately selected patients, arterial embolization appears to be an effective safe treatment for a GIST metastasis rupture.

Gender-dependent differences of mitochondrial function and oxidative stress in rat skeletal muscle at rest and after exercise training.

OBJECTIVE: This study investigated gender-dependent differences of mitochondrial function and sensitivity to in vitro ROS exposure in rat skeletal muscle at rest and after exercise training. METHODS: Wistar rats underwent running training for 6 weeks. In vitro measurements of hydroxyl radical production, oxygen consumption (under basal and maximal respiration conditions) and ATP production were made on permeabilized fibers. Mitochondrial function was examined after exposure and non-exposure to an in vitro generator system of reactive oxygen species (ROS). Antioxidant enzyme activities and malondialdehyde (MDA) content were also determined. RESULTS: Compared with sedentary males, females showed a greater resistance of mitochondrial function (oxygen consumption and ATP production) to ROS exposure, and lower MDA content and antioxidant enzyme activities. The training protocol had more beneficial effects in males than females with regard to ROS production and oxidative stress. In contrast to male rats, the susceptibility of mitochondrial function to ROS exposure in trained females was unchanged. DISCUSSION: Exercise training improves mitochondrial function oxidative capacities in both male and female rats, but is more pronounced in males as a result of different mechanisms. The resistance of mitochondrial function to in vitro oxidative stress exposure and the antioxidant responses are gender- and training-dependent, and may be related to the protective effects of estrogen.

When bone becomes marble: Head and neck manifestations of osteopetrosis.

Osteopetrosis is a genetically determined bone disease resulting from malfunction of osteoclastic activity, leading to excessive deposition of immature bone. This may result in complete agenesis of the paranasal sinuses, oral complications and multiple cranial neuropathies. The case of a 12-year-old boy with osteopetrosis is presented.

Effects of magnesium sulfate in kainic acid-induced status epilepticus.

Because magnesium has antiseizure effects in some animal models of epilepsy, and possible neuroprotective effects in some models of neuronal injury, we aimed to investigate its effects in the kainic acid (KA) model of status epilepticus (SE) in prepubescent rats. This age was chosen because it is a common age for onset of epilepsy and of SE in humans. Three groups of P35 rats were studied: Group I (MgKA) received magnesium sulfate MgSO4 (270 mg/kg then 27 mg/kg every 20 minutes for 5 hours) and 10 mg/kg KA. Group II (KA) received saline instead of MgSO4 and 10 mg/kg KA. Group III (control) received saline injections only. The dose we used has been shown previously to have anticonvulsant activity in another seizure model. Rats were recorded for their acute behavioral seizures directly after KA, and underwent the handling and Morris Water Maze (MWM) tests on P96-97 and P102-106 respectively. The MgKA and the KA groups did not differ in their acute seizures and both showed similar histologic lesions in CA3/CA4 and CA1 hippocampal subfields, and were more aggressive on the handling test than control rats. The MgKA group took more time to reach the platform in MWM than controls, while the KA group scores were intermediate between the two groups. Using the dose of 540 mg/kg MgSO4 and 54 mg/kg every 20 min showed the similar result of lack of protection against impairment in long-term memory. We conclude that (1) Magnesium did not manifest acute behavioral antiseizure effects in the KA P35 model of SE. (2) Magnesium did not prevent the tested long-term behavioral and histological consequences of SE in this model.

Effect of exercise training on oxidative stress and mitochondrial function in rat heart and gastrocnemius muscle.

OBJECTIVE: This study aimed to explore the effect of endurance training on oxidative parameters and mitochondrial function in gastrocnemius and heart muscle. METHODS: Male Wistar rats were trained by running for 6 weeks. In vitro measurements of the rates of hydroxyl radical ((•)OH) production, oxygen consumption (in either the absence, basal rate (V0), or the presence, maximal rate (Vmax), of adenosine diphosphate), and adenosine triphosphate (ATP) production were made simultaneously in permeabilized fibers. The mitochondrial function was explored after exposure or non-exposure to an in vitro generator system of reactive oxygen species (ROS). RESULTS: Vmax was not affected by training, but V0 decreased. In conditions of maximal mitochondrial functioning, an increase in ATP rate and a decrease in (•)OH production occurred simultaneously. In vitro ROS exposure disturbed mitochondrial function, but training modified the vulnerability of Vmax and ATP rate to ROS in different ways. DISCUSSION: We hypothesize that the part of Vmax devoted to proton leakage was decreased in trained rats, consequently improving ATP synthesis. The data suggest that, after training, there is more efficient use of electrons in respiratory chain energy production, rather than a greater ROS scavenging capacity.

Vocal cord paralysis after open-heart surgery.

Vocal cord paralysis is a known entity often described as a complication of neck surgery. A less frequent site of injury to the recurrent laryngeal nerve is the chest. The left side is usually more affected than the right side in view of its long intrathoracic segment. Only few cases of right vocal cord paralysis following open-heart surgery are reported in the literature. The purpose of this article is to review the common possible mechanisms of injury to the right recurrent laryngeal nerve following open-heart surgery in order to draw the attention of the caring physician to the clinical significance of such a complication. In fact, transient hoarseness following open-heart surgery may be an ominous sign of recurrent laryngeal nerve injury. It should not be assumed to be secondary to intralaryngeal edema. Several mechanisms of injury to the recurrent laryngeal nerve have been suggested: (1) through central venous catheterization; (2) by traction on the esophagus; (3) by direct vocal cord damage or palsy from a traumatic endotracheal intubation; (4) trauma by compression of the recurrent laryngeal nerve or its anterior branch at the tracheoesophageal groove by an inappropriately sized endotracheal tube cuff; (5) by a faulty insertion of a nasogastric tube; (6) median sternotomy and/or sternal traction pulling laterally on both subclavian arteries; (7) direct manipulation and retraction of the heart during open-heart procedures; (8) hypothermic injury with ice/slush. If vocal cord paralysis was overlooked as a possible complication of open-heart surgery, the patient may suffer from dysphonia in addition to problems of paramount importance such as inefficient cough and aspiration. Although it is true that the incidence of vocal cord paralysis remains very low, yet its presence is alarming and necessitates close follow up on the patient for the possible need of surgical intervention if recovery fails.

Bifocal Presentation of Primary Testicular Extranasal NK/T-Cell Lymphoma: A Case Report and Review of the Literature.

Introduction. Testicular lymphoma is an aggressive disease with a very poor prognosis. Nasal-type natural killer/T-cell lymphoma (NKTCL-N) in particular is very uncommon and has a rapidly progressive, fatal course. Case Report. We report a case of primary NKTCL-N of the testis in a 38-years-old Middle Eastern man. The patient had a history of primary right testicular tumor diagnosed at an outside institution as a seminoma and treated with orchiectomy followed by chemo/radiation. On admission, the patient had an enormous nasal granuloma with blood workup showing pancytopenia and elevated liver function tests due to active hepatitis B infection. CT scan of the sinuses showed a very large soft tissue mass, and PET scan showed splenomegaly with multiple lymph node masses in the pelvis and the chest areas. Bone marrow and nasal tumor biopsies as well as review of the slides from the initial orchiectomy were all in favor of NKTCL-N lymphoma. The patient was treated with CHOD based combination chemotherapy and responded dramatically to the first two cycles but passed away from fulminant hepatitis B infection. Conclusion. Despite all known treatments of NKTCL-N lymphoma of the testes, this disease has a very poor prognosis and invariably follows an aggressive clinical course.

Anatomic measurements for the endoscopic modified Lothrop procedure.

BACKGROUND: The aim of this study was to introduce preoperative radiographic frontal recess and sinus anatomic measurements to assist in the selection of patients considered for the modified Lothrop procedure. METHODS: Data were collected from sagittally reconstructed computed tomography (CT) scans of seven cadaver heads. Four anatomic parameters for measurement were defined as follows: (1) thickness of the nasal beak (desirable < 10 mm); (2) midsagittal distance from nasal beak to skull base (adding 1 and 2 provides the anterior-posterior (AP) space at the cephalad margin of the frontal recess; desirable, > or = 15 mm); (3) accessible dimension (in a parasagittal plane through the frontal ostium; the distance between two lines drawn parallel to the plane of the anterior skull base and perpendicular to the line of the insertion of the nasal endoscope during surgery; the posterior line is drawn at the skull base and the anterior line is drawn at the posterior margin of the nasal beak; the distance between the lines indicates the space available for instrumentation; desirable, > 5 mm); (4) AP dimension of each frontal sinus. RESULTS: The average and the range of each parameter measured were as follows: (1) nasal beak thickness = 8.0 mm (5.0-10.4 mm); (2) nasal beak-skull base = 7.9 mm (2.5-14.1 mm); (3) accessible dimension, 6.1 mm (0.9-9.6 mm); (4) AP diameter of the frontal sinus, 9.7 mm (5.2-14.1 mm). Four specimens were considered candidates for modified Lothrop and three were not. CONCLUSION: Preoperative radiographic frontal recess and sinus anatomic measurements may assist in the selection of patients considered for the endoscopic modified Lothrop procedure.

Hippocampal programmed cell death after status epilepticus: evidence for NMDA-receptor and ceramide-mediated mechanisms.

PURPOSE: Status epilepticus (SE) can result in acute neuronal injury with subsequent long-term age-dependent behavioral and histologic sequelae. To investigate potential mechanisms that may underlie SE-related neuronal injury, we studied the occurrence of programmed cell death (PCD) in the hippocampus in the kainic acid (KA) model. METHODS: In adult rats, KA-induced SE resulted in DNA fragmentation documented at 30 h after KA injection. Ceramide, a known mediator of PCD in multiple neural and nonneural tissues, increased at 2-3 h after KA intraperitoneal injection, and then decreased to control levels before increasing again from 12 to 30 h after injection. MK801 pretreatment prevented KA-induced increases in ceramide levels and DNA fragmentation, whether there was reduction in seizure severity or not (achieved with 5 mg/kg and 1 mg/kg of MK801, respectively). RESULTS: Both ceramide increases and DNA fragmentation were observed after KA-induced SE in adult and in P35 rats. Ceramide did not increase after KA-induced SE in P7 pups, which also did not manifest any DNA fragmentation. Intrahippocampal injection of the active ceramide analogue C2-ceramide produced widespread DNA fragmentation, whereas the inactive ceramide analogue C2-dihydroceramide did not. CONCLUSIONS: Our data support the hypotheses that (a) N-methyl-d-aspartate-receptor activation results in ceramide increases and in DNA fragmentation; (b) ceramide is a mediator of PCD after SE; and (c) there are age-related differences in PCD and in the ceramide response after SE. Differences in the ceramide response could, potentially, be responsible for observed age-related differences in the response to SE.

Effects of creatine and cyclocreatine supplementation on kainate induced injury in pre-pubescent rats.

PURPOSE: To investigate if energy precursor supplementation is neuroprotective in two neuroexcitotoxicity models; the kainate and the kainate followed by chronic phenobarbital models. METHODS: Rats in experiment 1 received 1% creatine or cyclocreatine chow from age (P) 21-65 days, underwent kainate induced status epilepticus on P35 and were compared, as adults, to kainate alone rats and to normal controls. Rats in experiment 2 received 1% creatine chow (P21-P85), underwent kainate status epilepticus on P35, received daily phenobarbital (or saline) injections (P36-P85) and were compared, as adults, to kainate, kainate-phenobarbital and to normal control rats that received regular chow. RESULTS: In experiment 1, the cyclocreatine-kainate group had increased emotionality and visuospatial learning deficits on the handling and watermaze tests as compared to all other groups. Creatine supplementation did not have any effects. In experiment 2, creatine supplementation did not prevent spontaneous recurrent seizures, aggressivity on the handling test or hippocampal histologic injury. CONCLUSION: Energy precursor supplementation in the doses used did not have neuroprotective effects in the kainate or kainate-phenobarbital models in pre-pubescent rats.