Subacute high-refined carbohydrate diet leads to abnormal reproductive control of the hypothalamic-pituitary axis in female rats.

We previously reported that female rats placed on a diet containing refined carbohydrates (HCD) resulted in obesity and reproductive abnormalities, such as high serum LH concentration and abnormal ovarian function. However, the impacts at the hypothalamic-pituitary (HP) function, specifically regarding pathways linked to reproductive axis modulation are unknown. In this study, we assessed whether subacute feeding with HCD results in abnormal reproductive control in the HP axis. Female rats were fed with HCD for 15 days and reproductive HP axis morphophysiology was assessed. HCD reduced hypothalamic mRNA expression (Kiss1, Lepr, and Amhr2) and increased pituitary LHß+ cells. These changes likely contribute to the increase in serum LH concentration observed in HCD. Blunted estrogen negative feedback was observed in HCD, with increased kisspeptin protein expression in the arcuate nucleus of the hypothalamus (ARH), lower LHß+ cells and LH concentration in ovariectomized (OVX)+HCD rats. Thus, these data suggest that HCD feeding led to female abnormal reproductive control of HP axis.

Subacute and low dose of tributyltin exposure leads to brown adipose abnormalities in male rats.

Tributyltin (TBT) is an obesogenic endocrine disrupting chemical (EDC) linked with several metabolic complications. Brown adipose tissue (BAT) is the principal site for thermogenesis, making it a potential target for obesity management and metabolic disease. However, few studies have evaluated TBT effect on BAT function. In this investigation, we assessed whether subacute (15 days) and low dose of TBT exposure (100 ng/kg/day) results in abnormal BAT morphophysiology in adult male rats. Body temperature, BAT morphology, inflammation, oxidative stress, collagen deposition and BAT metabolic gene expression markers were assessed in room temperature (Room, ∼24 ºC) and after cold tolerance test (Cold, ∼4 ºC) conditions. A reduction in body temperature was observed in both Room and Cold conditions in TBT rats, suggesting abnormal BAT thermogenic function. Changes in BAT morphology were observed in TBT rats, with an increase in BAT lipid accumulation, an increase in BAT unilocular adipocyte number and a decrease in BAT multilocular adipocyte number in Room condition. All these parameters were opposite in Cold condition TBT rats, leading to a borderline increase in BAT UCP1 protein expression. An increase in BAT mast cell number was observed in TBT rats in Room condition. An increase in ED1 protein expression (macrophage marker) was observed in TBT rats in Cold condition. Oxidative stress and collagen deposition increased in both Room and Cold conditions in TBT rats. TBT exposure caused a borderline increase in BAT COL1A1 protein expression in Cold condition. Further, strong negative correlations were observed between body temperature and BAT lipid accumulation, and BAT lipid accumulation and multilocular adipocyte number. Thus, these data suggest that TBT exposure impaired BAT morphophysiology through impacts on lipid accumulation, inflammation, fibrosis and oxidative stress in male rats.

High-refined carbohydrate diet alters different metabolic functions in female rats.

A diet containing refined carbohydrate (HCD) caused obesity and white adipose tissue (WAT) abnormalities, but it is unclear if HCD is linked with other metabolic dysfunctions in female models. Thus, we assessed whether HCD results in WAT, pancreas, liver, skeletal muscle (SM) and thyroid (TH) abnormalities in female rats. Female rats were fed with HCD for 15 days and metabolic morphophysiology, inflammation, oxidative stress (OS), and fibrosis markers were assessed. HCD rats presented large adipocytes, hyperleptinemia, and WAT OS. HCD caused irregular glucose metabolism, low insulin levels, and large pancreatic isle. Granulomas, reduced glycogen, and OS were observed in HCD livers. HCD caused hypertrophy and increased in glycogen in SM. HCD caused irregular TH morphophysiology, reduced colloid area and high T3 levels. In all selected tissues, inflammation and fibrosis were observed in HCD rats. Collectively, these data suggest that the HCD impairs metabolic function linked with irregularities in WAT, pancreas, liver, SM and TH in female rats.

Acute physiologic prediction of pediatric post-traumatic epilepsy.

OBJECTIVE: Post-traumatic epilepsy (PTE) is a known complication of traumatic brain injury (TBI). Limited physiologic biomarkers have been investigated in relation to pediatric PTE. Our aim is to identify clinical, physiologic and neuroimaging biomarkers predictive of pediatric PTE arising during the acute care phase after injury. METHODS: We performed a retrospective analysis from a prospectively collected clinical database of pediatric patients who underwent multimodality neurologic monitoring that included continuous electroencephalography and intracranial pressure (ICP) monitoring. Biomarkers included hemodynamic vital signs, model-based indices of cerebrovascular pressure reactivity (CVPR) and autonomic function (AF), electroencephalographic abnormalities, and neuroimaging abnormalities on the initial CT scan on day of imaging. Our primary outcome, PTE, was classified as the presence of unprovoked seizures 2 months post-injury or the continued need for antiseizure medications at 12-month post-injury. We utilized univariate logistic regression to identify biomarkers associated with PTE. RESULTS: 61 surviving patients were included in this study, among which 10 (16.4%) developed PTE. We identified that PTE was associated with increased ICP (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.02-1.52), increased pressure reactivity indices (92.53, 2.84->999.99), increased wavelet pressure reactivity indices (121.76, 2.84->999.99), increased CT Marshall scores (1.76, 1.13-2.74), decreased HRsd (0.54, 0.33-0.87) and the presence of epileptiform discharges (8.06, 1.85-35.17), and abnormal sleep spindles (4.88, 1.18-20.00). Whereas early post-traumatic seizures within the first 7 days post-injury were associated with PTE development (7.58, 1.81-39.68), this association was significant for such seizures occurring between 24 and 168 h post-injury (21.47, 4.18-110.38), and not for seizures occurring within 24 h post-injury. Among patients experiencing early post-traumatic seizures, increased time with seizures on surface electroencephalography was associated with PTE development (7.28, 2.05-73.14). We also identified that development of PTE was associated with worsened functional outcomes identified by increased Glasgow Outcome Scale - Extended Pediatric (GOSE-PEDs) scores (3.18, 1.68-8.01). CONCLUSION: Pediatric PTE development is associated with increased ICP, impaired CVPR, low heart rate variability, worsened neuroimaging findings, and electroencephalographic abnormalities identified during intensive care. Further studies are needed to investigate strategies to mitigate pediatric PTE development.

Tributyltin and high-refined carbohydrate diet lead to metabolic and reproductive abnormalities, exacerbating premature ovary failure features in the female rats.

Exposure to the obesogen tributyltin (TBT) alone or high carbohydrate diet (HCD) alone leads to obesity and reproductive complications, such as premature ovary failure (POF) features. However, little is known about interactions between TBT and nutrition and their combined impact on reproduction. In this study, we assessed whether acute TBT and HCD exposure results in reproductive and metabolic irregularities. Female rats were treated with TBT (100 ng/kg/day) and fed with HCD for 15 days and metabolic and reproductive outcomes were assessed. TBT and HCD rats displayed metabolic impairments, such as increased adiposity, abnormal lipid profile and triglyceride and glucose (TYG) index, worsening adipocyte hypertrophy in HCD-TBT rats. These metabolic consequences were linked with reproductive disorders. Specifically, HCD-TBT rats displayed irregular estrous cyclicity, high follicle-stimulating hormone (FSH) levels, low anti-Müllerian hormone (AMH) levels, reduction in ovarian reserve, and corpora lutea (CL) number, with increases in atretic follicles, suggesting that HCD-TBT exposure exacerbated POF features. Further, strong negative correlations were observed between adipocyte hypertrophy and ovarian reserve, CL number and AMH levels. HCD-TBT exposure resulted in reproductive tract inflammation and fibrosis. Collectively, these data suggest that TBT plus HCD exposure leads to metabolic and reproductive abnormalities, exacerbating POF features in female rats.

Effect of Verapamil, an L-Type Calcium Channel Inhibitor, on Caveolin-3 Expression in Septic Mouse Hearts.

Sepsis-induced myocardial dysfunction considerably increases mortality risk in patients with sepsis. Previous studies from our group have shown that sepsis alters the expression of structural proteins in cardiac cells, resulting in cardiomyocyte degeneration and impaired communication between cardiac cells. Caveolin-3 (CAV3) is a structural protein present in caveolae, located in the membrane of cardiac muscle cells, which regulates physiological processes such as calcium homeostasis. In sepsis, there is a disruption of calcium homeostasis, which increases the concentration of intracellular calcium, which can lead to the activation of potent cellular enzymes/proteases which cause severe cellular injury and death. The purpose of the present study was to test the hypotheses that sepsis induces CAV3 overexpression in the heart, and the regulation of L-type calcium channels directly relates to the regulation of CAV3 expression. Severe sepsis increases the expression of CAV3 in the heart, as immunostaining in our study showed CAV3 presence in the cardiomyocyte membrane and cytoplasm, in comparison with our control groups (without sepsis) that showed CAV3 presence predominantly in the plasma membrane. The administration of verapamil, an L-type calcium channel inhibitor, resulted in a decrease in mortality rates of septic mice. This effect was accompanied by a reduction in the expression of CAV3 and attenuation of cardiac lesions in septic mice treated with verapamil. Our results indicate that CAV3 has a vital role in cardiac dysfunction development in sepsis and that the regulation of L-type calcium channels may be related to its expression.

The impact of endocrine-disrupting chemical exposure in the mammalian hypothalamic-pituitary axis.

The hypothalamic-pituitary axis (HP axis) plays a critical and integrative role in the endocrine system control to maintain homeostasis. The HP axis is responsible for the hormonal events necessary to regulate the thyroid, adrenal glands, gonads, somatic growth, among other functions. Endocrine-disrupting chemicals (EDCs) are a worldwide public health concern. There is growing evidence that exposure to EDCs such as bisphenol A (BPA), some phthalates, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and biphenyls (PBBs), dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and atrazine (ATR), is associated with HP axis abnormalities. EDCs act on hormone receptors and their downstream signaling pathways and can interfere with hormone synthesis, metabolism, and actions. Because the HP axis function is particularly sensitive to endogenous hormonal changes, disruptions by EDCs can alter HP axis proper function, leading to important endocrine irregularities. Here, we review the evidence that EDCs could directly affect the mammalian HP axis function.

High-refined carbohydrate diet leads to polycystic ovary syndrome-like features and reduced ovarian reserve in female rats.

Obesity is associated with several female reproductive complications, such as polycystic ovary syndrome (PCOS). The exact mechanism of this relationship remains unclear. Few previous studies using diet containing refined carbohydrate (HCD) leading to obesity have been performed and it is unclear if HCD is linked with reproductive dysfunctions. In this investigation, we assessed whether subchronic HCD exposure results in reproductive and other irregularities. Female rats were fed with HCD for 15 days and metabolic outcomes and reproductive tract morphophysiology were assessed. We further assessed reproductive tract inflammation, oxidative stress (OS) and fibrosis. HCD rats displayed metabolic impairments, such as an increase in body weight/adiposity, adipocyte hypertrophic, abnormal lipid profile, glucose tolerance and insulin resistance (IR) and hyperleptinemia. Improper functioning of the HCD reproductive tract was observed. Specifically, irregular estrous cyclicity, high LH levels and abnormal ovarian morphology coupled with reduction in primordial and primary follicle numbers was observed, suggesting ovarian reserve depletion. Improper follicular development and a reduction in antral follicles, corpora lutea and granulosa layer area together with an increase in cystic follicles were apparent. Uterine atrophy and reduction in endometrial gland (GE) number was observed in HCD rats. Reproductive tract inflammation, OS and fibrosis were seen in HCD rats. Further, strong positive correlations were observed between body weight/adiposity and IR with estrous cycle length, cystic follicles, ovarian reserve, GE and other abnormalities. Thus, these data suggest that the subchronic HCD exposure led to PCOS-like features, impaired ovarian reserve, GE number, and other reproductive abnormalities in female rats.

Early single-dose treatment with exosomes provides neuroprotection and improves blood-brain barrier integrity in swine model of traumatic brain injury and hemorrhagic shock.

BACKGROUND: Administration of human mesenchymal stem cell (MSC)-derived exosomes can enhance neurorestoration in models of traumatic brain injury (TBI) and hemorrhagic shock (HS). The impact of early treatment with MSC-derived exosomes on brain injury in a large animal model remains unknown. We sought to evaluate the impact of early single-dose exosome treatment on brain swelling and lesion size, blood-based cerebral biomarkers, and blood-brain barrier (BBB) integrity. METHODS: Female Yorkshire swine were subjected to a severe TBI (12-mm cortical impact) and HS (40% estimated total blood volume). One hour into shock, animals were randomized (n = 5/cohort) to receive either lactated Ringer's (LR; 5 mL) or LR + exosomes (1 × 10 exosome particles in 5 mL LR). Animals then underwent additional shock (1 hour) followed by normal saline resuscitation. After 6 hours of observation, brain swelling (% increase compared with the uninjured side) and lesion size (mm) were assessed. Cerebral hemodynamics and blood-based biomarkers of brain injury were compared. Immunofluorescence and RNA sequencing with differential gene expression and pathway analysis were used to assess the integrity of the perilesion BBB. RESULTS: Exosome-treated animals had significantly less (p < 0.05) brain swelling and smaller lesion size. They also had significantly decreased (p < 0.05) intracranial pressures and increased cerebral perfusion pressures. Exosome-treated animals had significantly decreased (p < 0.05) albumin extravasation and significantly higher (p < 0.05) laminin, claudin-5, and zonula occludens 1 levels. Differential gene expression and pathway analysis confirmed these findings. Serum glial fibrillary acidic protein levels were also significantly lower (p < 0.05) in the exosome-treated cohort at the end of the experiment. CONCLUSION: In a large animal model of TBI and HS, early treatment with a single dose of MSC-derived exosomes significantly attenuates brain swelling and lesion size, decreases levels of blood-based cerebral biomarkers, and improves BBB integrity.

[Treatment management of a case of class I bialveolar protrusion with mouth breathing]. / Gestion du traitement d'un cas de classe I biproalvéolie avec ventilation buccale.

This is the case of a 12-year-old African young girl with bialveolar protrusion and night mouth breathing. Orthodontic treatment without dental extraction consisted after tonsillectomy in retraction of anterior teeth in the diastema spaces. The normalization of the angle of the upper incisor has improved bialveolar protrusion without alteration to the prior balance of soft tissue.

[Two clinical examples of the use of orthodontic mini-screws]. / Deux exemples cliniques de l'utilisation des mini-vis orthodontiques.

Orthodontic needs to reply on a reliable anchoring as fixed as possible to ensure the best orthodontic movements. The orthodontic mini-screws provide a fixed anchorage for performing movements and treatments considered until then to be difficult or even impossible, particularly the treatment of ingression in the posterior area. The orthodontic anchorage mini-screw has the advantage of being cheaper, easier to place and do not require surgical procedure. This article illustrates two clinical indications of orthodontic mini-screws namely the intrusion of incisors and cross tooth movement.

[Transient removable dentures]. / Les prothèses amovibles transitoires.

Removable dentures are always transient current. The epidemiology and causes of tooth gaps demonstrate the need to master the different prosthetic treatment. This made whether to propose treatment plans that take into account psychological, physiological and technical support for this patient. Different situations may arise. A gradual transition may be considered or immediate passage to the total edentulous according to general criteria, local and desiderata of patients. After tooth extraction, the transitional prosthesis can control bone lysis thereby it is part of a complete treatment before prosthesis. It also facilitates a good psychological and physiological integration before the prosthesis use.

Acute macular neuroretinopathy associated with the use of norepinephrine reuptake inhibitors: a case series and OCT findings.

PURPOSE: The purpose of this study was to report a case series of patients with acute macular neuroretinopathy in which patients concomitantly used oral norepinephrine reuptake inhibitors. METHODS: Retrospective case review. PATIENTS: Three patients with retinal findings consistent with acute macular neuroretinopathy are presented. CONCLUSION: The use of oral neuromodulators should be considered in cases of acute macular neuroretinopathy.

Health-related quality of life and dialysis dependence in critically ill patient survivors of acute kidney injury.

BACKGROUND: Acute kidney injury is a common disorder in critical ill patients and it is associated with high mortality. Few studies focus on long-term perspectives such as health-related quality of life (HRQOL) and dialysis dependence. METHODS: Prospective cohort study at the intensive care unit (ICU) of a Brazilian tertiary hospital. All patients requiring dialysis over a 2-year enrollment period were included. The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) assessed the HRQOL along with patient status and dialysis dependence. RESULTS: 408 patients (11%) required dialysis. ICU, hospital, and after-hospital cumulative fatality rates were 70%, 74%, and 80%, respectively. A total of 68 of 82 eligible patients were interviewed in an average of 256 days after hospital discharge, while 8 patients (11.8%) were in regular dialysis. There was no association between Acute Physiology and Chronic Health Evaluation II score, use of vasopressors, mechanical ventilation, creatinine, number of dialysis, and SF-36 scores. Better HRQOL was associated with previous conditions, as younger age and no chronic kidney disease; condition related to severity of acute illness, as have not had sepsis, short period at ICU, and hospital; and conditions after discharge, considered working currently. CONCLUSIONS: Previous chronic kidney disease was strongly associated with permanence in dialysis and lower further HRQOL. Younger survivors who have not had sepsis or long stays at hospitals, able to return to their jobs, had better HRQOL.

Diffuse retinal pigment epithelial disease in an adult with cystic fibrosis.

An adult with cystic fibrosis presented for decreased vision in the right eye of several months' duration. Biomicroscopy and fluorescein angiography demonstrated bilateral large subretinal drusenoid deposits concentrated temporal to the fovea, as well as a small subretinal hemorrhage associated with focal leakage of fluid within the macula in the right eye. Optical coherence tomography demonstrated subretinal fluid consistent with choroidal neovascular membrane in the right eye with the absence of fluid in the left eye. The retinal manifestations of bilateral diffuse drusen associated with choroidal neovascular membrane may be consistent with autosomal dominant drusen, age-related macular degeneration, and type II glomerulonephritis, or alternatively may be a unique finding associated with cystic fibrosis. To the authors' knowledge, these findings have not previously been described in association with cystic fibrosis.

[Role of the combination of external radiotherapy--partial cystectomy--interstitial brachytherapy in pT1 G3, pT2 and pT3 bladder tumors]. / Place de l'association radiothérapie externe--cystectomie partielle--brachythérapie interstitielle dans les tumeurs de vessie pT1 G3, pT2 et pT3.

Although it is still the reference method for curative treatment of invasive bladder cancer, radical cystectomy is a major surgical procedure justifying the evaluation of surgical tumoral excision in combination with curietherapy. At Nice University Hospital, between 1986 and 1998, 29 men with invasive bladder cancer were treated by partial cystectomy and interstitial brachytherapy. All the patients received external preoperative radiation of the pelvis of 10.5 Gy (Three 3.5 Gy flashes) three days before partial cystectomy associated with implantation of curietherapy guides carried out on average Five days after surgery with the dose of 50 Gy. After between 5 to 17 years of follow-up, eight deaths out of 14 occurred due to the disease and/or treatment, three patients had a superficial recurrence and one patient underwent salvage prostatocystectomy. Curietherapy gave rise to no direct complications, three patients suffered an eventration and 1 evisceration. Two out of 15 surviving patients suffer from invalidating pollakiuria and one from chronic retention. This study shows that overall survival corrected for intercurrent deaths is lower than data in the literature, though the low sample size makes it impossible to compare the carcinological results and survival per pT category. In addition, this strategy results in fewer complications after radiation therapy. Hence, although a certain number of questions remain unanswered, it seems possible for suitably selected patients to expect the same cure rates as radical surgery with reduced morbidity.

Meckel's diverticulum and laparoscopy of children. What's new?

Laparoscopy has not changed the diagnostic approach in Meckel's diverticulum (MD). Preoperative echography and scintigraphy are still indicated in case of symptomatic diverticulum. During each submesocolic laparoscopy we must meticulously look for Meckel's diverticulum. There are two surgical procedures for MD resection: 1. Short intestinal resection after exteriorization (celio-assisted surgery) is advocated in young patients or in complicated MD. 2. Laparoscopic resection by the Endo GIA stapler is advocated in older patients and latent MD with a narrow base.

Retroperitoneal laparoscopic nephrectomy in children. Preliminary report of 18 cases.

Laparoscopic nephrectomy is a new procedure which remains to be evaluated in adults and children. This technique enables the reduction of parietal complications and sequelae. The majority of indications, e.g. renal dysplasia, destroyed kidneys due to obstructive or refluxing uropathy, are suitable for laparoscopic nephrectomy. Contraindications are Wilm's tumor and trauma which represent only 20% of nephrectomies in our experience. As in open surgery, a retroperitoneal approach seems more logical and better adapted than a transperitoneal approach to perform nephroureterectomy for benign disease. From August 1993 to December 1995, we attempted 18 retroperitoneal laparoscopic nephrectomies in children aged from 3 months to 14 years. The patient is placed in a lateral position, and after creation of a retropneumoperitoneum under direct vision control without balloon dissection, three or four ports are needed, renal vessels are dissected, then clipped or coagulated if small. Destroyed kidneys are generally of small size, so they can be extracted via a 10- or 12-mm cannula site without morcellation. Operative time is 35-210 min (median 106 min). There were no major complications and only one conversion. In conclusion, retroperitoneal laparoscopic nephrectomy in children is a feasible and safe procedure in well-trained hands.