Association of Obesity and Diabetes With the Incidence of Breast Cancer in Louisiana.

INTRODUCTION: Breast cancer is a heterogeneous disease, consisting of multiple molecular subtypes. Obesity has been associated with an increased risk for postmenopausal breast cancer, but few studies have examined breast cancer subtypes separately. Obesity is often complicated by type 2 diabetes, but the possible association of diabetes with specific breast cancer subtypes remains poorly understood. METHODS: In this retrospective case-control study, Louisiana Tumor Registry records of primary invasive breast cancer diagnosed in 2010-2015 were linked to electronic health records in the Louisiana Public Health Institute's Research Action for Health Network. Controls were selected from Research Action for Health Network and matched to cases by age and race. Conditional logistic regression was used to identify metabolic risk factors. Data analysis was conducted in 2020‒2021. RESULTS: There was a significant association between diabetes and breast cancer for Luminal A, Triple-Negative Breast Cancer, and human epidermal growth factor 2‒positive subtypes. In multiple logistic regression, including both obesity status and diabetes as independent risk factors, Luminal A breast cancer was also associated with overweight status. Diabetes was associated with increased risk for Luminal A and Triple-Negative Breast Cancer in subgroup analyses, including women aged ≥50 years, Black women, and White women. CONCLUSIONS: Although research has identified obesity and diabetes as risk factors for breast cancer, these results underscore that comorbid risk is complex and may differ by molecular subtype. There was a significant association between diabetes and the incidence of Luminal A, Triple-Negative Breast Cancer, and human epidermal growth factor 2‒positive breast cancer in Louisiana.

Comparison of weight loss data collected by research technicians versus electronic medical records: the PROPEL trial.

BACKGROUND/OBJECTIVES: Pragmatic trials are increasingly used to study the implementation of weight loss interventions in real-world settings. This study compared researcher-measured body weights versus electronic medical record (EMR)-derived body weights from a pragmatic trial conducted in an underserved patient population. SUBJECTS/METHODS: The PROPEL trial randomly allocated 18 clinics to usual care (UC) or to an intensive lifestyle intervention (ILI) designed to promote weight loss. Weight was measured by trained technicians at baseline and at 6, 12, 18, and 24 months. A total of 11 clinics (6 UC/5 ILI) with 577 enrolled patients also provided EMR data (n = 561), which included available body weights over the period of the trial. RESULTS: The total number of assessments were 2638 and 2048 for the researcher-measured and EMR-derived body weight values, respectively. The correlation between researcher-measured and EMR-derived body weights was 0.988 (n = 1 939; p < 0.0001). The mean difference between the EMR and researcher weights (EMR-researcher) was 0.63 (2.65 SD) kg, and a Bland-Altman graph showed good agreement between the two data collection methods; the upper and lower boundaries of the 95% limits of agreement are -4.65 kg and +5.91 kg, and 71 (3.7%) of the values were outside the limits of agreement. However, at 6 months, percent weight loss in the ILI compared to the UC group was 7.3% using researcher-measured data versus 5.5% using EMR-derived data. At 24 months, the weight loss maintenance was 4.6% using the technician-measured data versus 3.5% using EMR-derived data. CONCLUSION: At the group level, body weight data derived from researcher assessments and an EMR showed good agreement; however, the weight loss difference between ILI and UC was blunted when using EMR data. This suggests that weight loss studies that rely on EMR data may require larger sample sizes to detect significant effects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number NCT02561221.

The effectiveness and adverse effects of D-cycloserine compared with placebo on social and communication skills in individuals with autism spectrum disorder.

BACKGROUND: Symptoms of autism spectrum disorder (ASD) have been associated, in part, with the dysfunction of N-methyl-D-aspartate (NMDA) glutamate receptors at excitatory synapses and glutamate abnormalities. Medications related to glutamatergic neurotransmission, such as D-cycloserine - which is a partial agonist of the NMDA glutamate receptor - are potential treatment options for the core features of ASD. However, the potential effect of D-cycloserine on the social and communication skills deficits of individuals with ASD has not been thoroughly explored and no systematic reviews of the evidence have been conducted. OBJECTIVES: To assess the efficacy and adverse effects of D-cycloserine compared with placebo for social and communication skills in individuals with ASD. SEARCH METHODS: In November 2020, we searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers. We also searched the reference lists of relevant publications and contacted the authors of the included study, Minshawi 2016, to identify any additional studies. In addition, we contacted pharmaceutical companies, searched manufacturers' websites and sources of reports of adverse events.  SELECTION CRITERIA: All randomised controlled trials (RCTs) of any duration and dose of D-cycloserine, with or without adjunct treatment, compared to placebo in individuals with ASD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted relevant data, assessed the risk of bias, graded the certainty of the evidence using the GRADE approach, and analysed and evaluated the data. We provide a narrative report of the findings as only one study is included in this review. MAIN RESULTS: We included a single RCT (Minshawi 2016) funded by the United States Department of Defense. It was conducted at two sites in the USA: Indiana University School of Medicine and Cincinnati Children's Hospital Medical Centre. In the included study, 67 children with ASD aged between 5 and 11 years were randomised to receive either 10 weeks (10 doses) of (50 mg) D-cycloserine plus social skills training, or placebo plus social skills training. Randomisation was carried out 1:1 between D-cycloserine and placebo arms, and outcome measures were recorded at one-week post-treatment. The 'risk of bias' assessment for the included study was low for five domains and unclear for two domains. The study (67 participants) reported low certainty evidence of little to no difference between the two groups for all outcomes measured at one week post-treatment: social interaction impairment (mean difference (MD) 3.61 (assessed with the Social Responsiveness Scale), 95% confidence interval (CI) -5.60 to 12.82); social communication impairment (MD -1.08 (measured using the inappropriate speech subscale of the Aberrant Behavior Checklist (ABC)), 95% CI -2.34 to 0.18); restricted, repetitive, stereotyped patterns of behaviour (MD 0.12 (measured by the ABC stereotypy subscale), 95% CI -1.71 to 1.95); serious adverse events (risk ratio (RR) 1.11, 95% CI 0.94 to 1.31); non-core symptoms of ASD (RR 0.97 (measured by the Clinical Global Impression-Improvement scale), 95% CI 0.49 to 1.93); and tolerability of D-cycloserine (RR 0.32 (assessed by the number of dropouts), 95% CI 0.01 to 7.68).  AUTHORS' CONCLUSIONS: We are unable to conclude with certainty whether D-cycloserine is effective for individuals with ASD. This review included low certainty data from only one study with methodological issues and imprecision. The added value of this review compared to the included study is we assessed the risk of bias and evaluated the certainty of evidence using the GRADE approach. Moreover, if we find new trials in future updates of this review, we could potentially pool the data, which may either strengthen or decrease the evidence for our findings.

Social cognition evolves: illustrations from our work on intergroup bias and on healthy adaptation / La Cognición Social evoluciona: ilustraciones de nuestro trabajo sobre Sesgo Intergrupal y Adaptación Saludable

When we first wrote Social Cognition (1984), social psychology's crisis critiqued methods, replicability, theory, and relevance. Social cognition research illustrates four phases of response to these challenges. First, the Cognitive Miser approach introduced methods less prone to experimenter or participant interference: looking time as attention, categorical memory for who said what. Next, the Motivated Tactician approach addressed replicability by identifying moderator variables, primarily goals and motivations. For example, interdependence (Fiske) and threat (Taylor) are prominent motivations in our respective research. The third wave, perceivers as Activated Actors, translated mental states to behavior, using theory-guided prediction. In intergroup bias, for example, Fiske's Stereotype Content Model predicts patterns of discriminatory behavior distinctive to each combination of stereotypic warmth and competence. Going beyond reported behavior, distinctive activations emerged in brain-imaging and muscle responses. In health psychology, Taylor's Positive Illusions theory predicts people cope with life-threatening illness by viewing the odds optimistically, the self positively, and possible control affirmatively. Again, the social cognitive processes interplay with psycho-physiology. Recently, social cognitive approaches have increasingly addressed inequality: health disparities, bias interventions, power dynamics, class effects, social morality, and intent inferences. Viewing perceivers as Inequality Enablers answers any remaining doubts about the field's continuing relevance

Cuando escribimos por primera vez Social Cognition (1984), la crisis de la psicología social cuestionaba los métodos, la replicabilidad, la teoría y la relevancia. La investigación sobre cognición social presenta cuatro fases en respuesta a estos desafíos. En primer lugar, el enfoque de la Avaricia Cognitiva introdujo métodos menos propensos a la interferencia del experimentador o del participante: considerar el tiempo como atención, o la memoria categórica para quién dijo qué. Posteriormente, el enfoque de la Motivación Táctica abordó la replicabilidad, al identificar variables moderadoras, principalmente objetivos y motivaciones. Por ejemplo, la interdependencia (Fiske) y la amenaza (Taylor) son motivaciones prominentes en nuestra respectiva investigación. Durante la tercera ola, los perceptores como Actores Activados transformaron los estados mentales en comportamiento, utilizando predicciones guiadas por la teoría. En el sesgo intergrupal, por ejemplo, el Modelo de Contenido de Estereotipos de Fiske predice patrones de comportamiento discriminatorio diferentes para cada combinación de calidez y competencia estereotípicas. Yendo más allá de la conducta manifiesta, surgieron activaciones distintivas en imágenes cerebrales y respuestas musculares. En psicología de la salud, la teoría de las Ilusiones Positivas de Taylor predice que las personas se enfrentan con las enfermedades mortales viendo las posibilidades de manera optimista, su autoimagen positivamente, y el posible control afirmativamente. Nuevamente, los procesos cognitivos sociales interactúan con la psicofisiología. Recientemente, los enfoques cognitivos sociales han abordado la desigualdad: desigualdades en salud, intervenciones sesgadas, dinámicas de poder, efectos de clase, moralidad social, e inferencias intencionadas. Considerando a los perceptores como Facilitadores de la Desigualdad responde cualquier duda que pudiese quedar acerca de la relevancia de este campo en la actualidad

A brief review of common mathematical calculations in therapeutic apheresis.

Apheresis is defined as the removal of blood from the body, its separation into constituent components, and removal or manipulation of one of these components prior to intravascular return with or without the addition of replacement fluid. Patients undergoing therapeutic apheresis often have multiple comorbidities, potentially affecting their hemodynamic status. Thus, a thorough understanding of apheresis principles and calculations is required for the performance of safe, efficacious, and successful procedures. The performance of simple transfusions or red blood cell exchange procedures is additionally complicated by the difficulties inherent in the procurement of compatible blood products, and the emphasis on minimizing exposure to unnecessary blood products. It is essential that apheresis physicians be able to accurately evaluate the risks/benefits inherent in the procedural options and efficiently stratify patients to the optimal therapeutic modality. The formulas requisite for performing therapeutic apheresis calculations are herein reviewed.

First detection of the mcr-1 colistin resistance gene in Escherichia coli from a patient with urinary tract infection in Myanmar.

Colistin-resistance gene mcr-1 was detected in an Escherichia coli sample among 442 clinical isolates collected in a tertiary-care hospital in Yangon, Myanmar, in 2018. This isolate was classified into phylogroup A-ST23 complex and harboured bla CTX-M-15 and bla TEM-1, associated with multiple mutations in quinolone-resistance-determining regions in gyrA and parC.

Nasal septal body and inferior turbinate sizes differ in subjects grouped by sex and age.

OBJECTIVES: To compare the size of the nasal septal body (SB) and inferior turbinate (IT) of subjects grouped by sex and age. METHOD: We measured SB and IT areas (in cm2) bilaterally in computed tomography (CT) sections of 150 para nasal sinuses from 72 males and 78 females. RESULTS: The right and left SB areas were smaller in females than in males. In the s25-year-old group, the right IT (RIT) was significantly smaller in females than in males. In the 26-35 and 46-45 age groups, the right SB (RSB) was significantly smaller in females than in males. CONCLUSION: The nasal SB may play a role in nasal physiology similar to a turbinate and help support optimal airflow. The vascular and glandular structures of the SB should be investigated in detail, and minimal invasive procedures should be performed in nasal surgery to avoid damaging essential structures.

Effects of indoor swimming pools on the nasal cytology of pool workers.

OBJECTIVE: We aimed to evaluate the relationship between swimming pool pollutants and allergic rhinitis in swimming pool workers. MATERIALS AND METHODS: Twenty-seven indoor pool workers (group 1) and 49 control subjects (group 2) were enrolled in the study. A skin prick test was performed and a nasal smear was obtained from each subject to evaluate rhinitis. RESULTS: When the groups were compared in terms of epithelial cells, group 1 had significantly more epithelial cells than group 2. When the groups were compared with regard to eosinophils, group 1 had significantly more eosinophils than group 2. The skin prick test results for both groups were not significantly different. CONCLUSION: Indoor pool workers showed severe symptoms of rhinitis and eosinophilic nasal cytology, likely due to chlorine. Nasal cytology is an easy-to-administer diagnostic test and can be used to follow up rhinitis in indoor pool workers, along with nasal endoscopy, a detailed clinical history and a skin prick test.

Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam.

BACKGROUND: Prior to 2007, highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses. METHODS AND FINDINGS: Respiratory specimens from patients suspected to be infected with avian influenza in 2007 were screened by influenza and H5 subtype specific polymerase chain reaction. Isolated H5N1 strains were further characterized by genome sequencing and drug susceptibility testing. Eleven poultry outbreak isolates from 2007 were included in the sequence analysis. Eight patients, all of them from northern Vietnam, were diagnosed with H5N1 in 2007 and five of them died. Phylogenetic analysis of H5N1 viruses isolated from humans and poultry in 2007 showed that clade 2.3.4 H5N1 viruses replaced clade 1 viruses in northern Vietnam. Four human H5N1 strains had eight-fold reduced in-vitro susceptibility to oseltamivir as compared to clade 1 viruses. In two poultry isolates the I117V mutation was found in the neuraminidase gene, which is associated with reduced susceptibility to oseltamivir. No mutations in the M2 gene conferring amantadine resistance were found. CONCLUSION: In 2007, H5N1 clade 2.3.4 viruses replaced clade 1 viruses in northern Vietnam and were susceptible to amantadine but showed reduced susceptibility to oseltamivir. Combination antiviral therapy with oseltamivir and amantadine for human cases in Vietnam is recommended.

Effect of aging on the distribution of basic fibroblast growth factor immunoreactive cells in the rat hippocampus.

Hippocampal formation is extremely sensitive to the aging process and appears to be one of the first regions to show structural and physiological changes with advancing age. Basic fibroblast growth factor (bFGF) plays an important role in the stimulation of mitogenesis in glial cells, the support of neuronal survival and the promotion of neurite outgrowth in vitro. In the present study, the effect of aging on the distribution of bFGF immunoreactive (bFGF-ir) cells was investigated. The protein product of bFGF was visualized immunohistochemically in the dorsal hippocampus of Wistar albino rats. bFGF-ir astrocytes in different subfields of hippocampus and neurons in CA2 field were quantified to determine whether changes in immunoreactivity were correlated with advancing age. Aging was accompanied by a decrease in bFGF-ir cell density in subfields of hippocampus. We concluded that aging was associated with a reduction in bFGF-ir cell density that may reflect a decreased expression of bFGF in the rat hippocampus.

The effects of quantum energy surgical device and of bipolar coagulation: a comparative experimental study.

OBJECTIVE: The quantum energy surgical device (QESD) employs an innovative, "no-touch" thermal coagulation, incision and evaporation technique in which thermal energy is delivered to tissue in the format of high-energy neutral argon gas atoms. The aim of this study is to compare QESD and bipolar coagulation (BC) through assessment of both haemostasis and histological damage to isolated femoral arteries of rats. METHODS: Sixty rats were randomly divided into acute and short-term experimental groups. In the acute group (n=20) histopathological evaluation was performed immediately following coagulation, whereas in the short-term experimental group (n=20) the evaluation was performed 10 days later. Each sham group consisted of ten rats. Viewed under the surgical microscope, only normal-appearing, freshly sectioned, and bleeding femoral arteries were studied. Right femoral arteries subject to QESD coagulation, and left femoral arteries to BC. Haemorrhaging was controlled using the minimal coagulation time necessary to stop it. All vascular layers, including endothelium, internal elastic lamina, media and adventitia were examined histologically and ultrastructurally in a "blind" fashion to critically compare morphological damage due to QESD and BC. RESULTS: Surgical haemostasis induced by QESD was found to be as safe as BC. Light microscopy revealed more marked histopathological changes in the BC than in the QESD group. These involved mainly the endothelial and medial compartments and, at the ultrastructural level, consisted of endothelial degeneration and exfoliation, irregularity of internal elastic lamina, degeneration, and loss of medial smooth muscle. CONCLUSION: The results indicate that QESD coagulation induces significantly less histological damage than does BC. Thus QESD coagulation is a safe, less tissue destructive, and equally effective method of haemostasis.

Morphological examination of the effects of defibrotide on experimentally induced bladder injury and its relation to interstitial cystitis.

This morphological study aims to investigate the effects of defibrotide, a deoxyribonucleic acid derivative drug with cytoprotective, immunosuppressive and vasorelaxant effects, on protamine sulfate induced bladder injury. Wistar albino female rats were catheterized and intravesically infused with phosphate buffered solution (control group) or, either protamine sulfate (bladder injury group) or protamine sulfate+defibrotide (bladder injury+defibrotide group) dissolved in phosphate buffered solution. The morphology of the urinary bladder was investigated using light and electron microscopy. The number of mast cells in the mucosa, mucosal alterations, intercellular junctions, surface topography and the glycosaminoglycan (GAG) layer as well as microvillus formation on the luminal surface were evaluated. In the bladder injury group, ulcerated areas, irregularity of the GAG layer, increased number of mast cells, vacuole formation, dilated perinuclear cistern, formation of pleomorphic and uniform microvilli and dilatations in the intercellular spaces in the urothelium were observed. In the bladder injury+defibrotide group a relatively normal urothelial topography, GAG layer and a few mast cells in the mucosa, some dilatations between the intercellular areas, less uniform microvilli, regular perinuclear cistern and tight junctions were observed. These results show that defibrotide can inhibit PS induced bladder damage.

Early histological changes of ileal mucosa after augmentation cystoplasty.

Segments of bowel are used routinely for transplantation in various pathological conditions such as contracted bladders or poorly compliant neuropathic bladders. However, little is known how these intestinal segments adopt to a toxic environment caused by urine. Therefore, the present study was performed to determine early histological changes of ileal mucosa after augmentation cystoplasty. Seven patients with augmentation cystoplasty underwent random cold-cup biopsies of ileal segments after a mean period of 14.4 months after cystoplasty and morphological changes were evaluated using light microscopy and transmission and scanning electron microscopy. Most pronounced features were varying degrees of villous atrophy, increased numbers of Paneth and goblet cells. Severity of atrophic villous changes were not related to the length of the interval between surgery and endoscopic biopsy. These findings may be explained as adaptations of bowel tissue to counteract noxious effects of urine and to maintain its epithelial function in the bladder.

The afferent connections of the posterior hypothalamic nucleus in the rat using horseradish peroxidase.

The posterior hypothalamic nucleus has been implicated as an area controlling autonomic activity. The afferent input to the nucleus will provide evidence as to its role in autonomic function. In the present study, we aimed to identify the detailed anatomical projections to the posterior hypothalamic nucleus from cortical, subcortical and brainstem structures, using the horseradish peroxidase (HRP) retrograde axonal transport technique in the rat. Subsequent to the injection of HRP into the posterior hypothalamic nucleus, extensive cell labelling was observed bilaterally in various areas of the cerebral cortex including the cingulate, frontal, parietal and insular cortices. At subcortical levels, labelled cells were observed in the medial and lateral septal nuclei, the bed nucleus of stria terminalis, and various thalamic and amygdaloid nuclei. Also axons of the vertical and horizontal limbs of the diagonal band were labelled and labelled cells were localised at the CA1 and CA3 fields of the hippocampus and the dentate gyrus. The brainstem projections were from the medial, lateral and parasolitary nuclei, the intercalated nucleus of the medulla, the sensory nuclei of the trigeminal nerve, and various reticular, vestibular, raphe and central grey nuclei. The posterior hypothalamic nucleus also received projections from the lateral and medial cerebellar nuclei and from upper cervical spinal levels. The results are discussed in relation to the involvement of the posterior hypothalamic nucleus in autonomic function and allows a better understanding of how the brain controls visceral function.

Eversion with four sutures: an easy, fast, and reliable technique for microvascular anastomosis.

In this study, a microvascular anastomosing technique called "eversion with four sutures" is introduced. For microvascular anastomosis, this technique requires fishmouth incisions at both vessel ends and the completion of four sutures. In 120 Wistar-Albino rats, 120 eversion and 120 conventional anastomoses were done in 240 femoral arteries. Each rat received both treatments. Operating time, bleeding time, number of sutures used, patency rates, and pseudoaneurysm formation were analyzed statistically; healing was evaluated with both light and electron microscopy. When compared with the conventional technique using nine sutures, the eversion with four sutures technique was found to be a faster and easier method of anastomosis and as reliable as the conventional technique. Without compromising patency rates, bleeding time, or rates of pseudoaneurysm formation, anastomosis time and amount of suture material exposed to the lumen were significantly reduced when using this technique. In conclusion, the authors think that eversion with four sutures is a reliable alternative to the conventional suturing technique, especially for emergency cases that require multiple microvascular anastomoses.

Cerebellar connections to the dorsomedial and posterior nuclei of the hypothalamus in the rat.

The stimulation or ablation of cerebellar structures has produced a variety of visceral responses, indicating a cerebellar role in visceral functions. Studies using anterograde and retrograde tracing methods have revealed connections between the hypothalamus and cerebellar structures. The aim of this study is to investigate the cerebellar connections of the dorsomedial (DMH) and posterior hypothalamic nuclei using retrograde axonal transport of horseradish peroxidase (HRP). In the present study, micro-injection of HRP restricted within the borders of the DMH showed that the projections of this nucleus are not uniform throughout its extent. The posterior DMH receives projections from the cerebellum, whereas the anterior DMH does not. These projections were from the (greatest to least concentration) lateral (dentate), anterior interposed (emboliform), and medial (fastigial) cerebellar nuclei. In addition, both the anterior and posterior DMH receive projections from various areas of the brainstem which confirms earlier studies and provides detailed descriptions. This study also demonstrates the distribution of labelled neurons to cerebellar and brainstem nuclei following HRP injection into the posterior hypothalamic nucleus. It provides clear evidence for a direct cerebellar nuclei-posterior DMH and cerebellar nuclei-posterior hypothalamic nucleus connections. We suggest that the brainstem reticular nuclei and other connections, such as the solitary, trigeminal and vestibular nuclei, of both DMH and posterior hypothalamus may contribute to the indirect cerebellohypothalamic connections. These observations offer a new perspective on the question of how the cerebellum may influence autonomic activity.

The effect of alpha-melanocyte stimulating hormone on endotoxin-induced intestinal injury.

We investigated the effect of alpha-melanocyte stimulating hormone (alpha-MSH) on endotoxin-induced intestinal inflammation and the role of nitric oxide and prostaglandins in this response. alpha-MSH treatment (25 microg/rat, intraperitoneally (i.p.); twice daily) reduced the severity of the lesions macroscopically and microscopically. This protective effect was found to be confined mainly to the distal ileum. These lesions were reversed by pretreatment with the non-selective COX inhibitor indomethacin (10 mg/kg, subcutaneously (s.c.)) but not by the selective COX-2 inhibitor nimesulide (3 mg/kg, s.c.), the NO donor sodium nitroprusside (4 mg/kg, i.v.) or the iNOS inhibitor dexamethasone (3 mg./kg, i.p.) at macroscopic level and reversed by Indo or Dex at microscopic level. Increased peroxidase activity -index of tissue neutrophil infiltration- in the distal ileum of LPS-treated rats was decreased by alpha-MSH and this effect was reversed by pretreatment with Indo. In conclusion, the neuropeptide alpha-MSH has a beneficial effect on endotoxin-induced distal intestinal lesions by a mechanism which probably involves nitric oxide and COX-1 derived prostaglandins.

The effect of tizanidine on chronic vasospasm in rats.

BACKGROUND: Cerebral vasospasm after subarachnoid hemorrhage (SAH) has remained a major cause of morbidity and mortality in patients with SAH. Excitatory neurotransmitters are gathered in the extracellular space during ischemia due to cerebral vasospasm and initiate or stimulate a series of pathophysiological biochemical processes which consequently lead to neuronal death. Tizanidine (Sandoz compound DS 103-282, 5-chloro-4,2 (2-imidazolin-2-yl-amino)-2,1,3-benzothiazol hydrochloride) is a centrally-acting muscle relaxant and a selective alpha 2 adrenoreceptor agonist which shows its effect by stimulating presynaptic alpha 2 adrenoreceptors in central ASPergic and GLUergic system by inhibiting aspartic acid and glutamic acid release. In this study, the effect of Tizanidine on vasospasm was evaluated. METHODS: We used a femoral artery vasospasm model in rats which has been described by Okada et al. 60 rats were examined in three groups. The first group was used as control group (Control) (n = 20), in the second group subarachnoid hemorrhage was performed (SAH) (n = 20), in the third group Tizanidine was administered in addition to SAH (SAH + Tizanidine administration) (n = 20). Animals in SAH + Tizanidine administration group received 0.3 mg/kg/day intraperitoneally for 7 days. Seven days after the experiment, after perfusion-fixation, 10 mm segments of both femoral arteries were removed and the femoral artery was prepared for light microscope examination, scanning and transmission electron microscopy and for morphometric analysis. RESULTS: There was a statistically significant difference between the electron, scanning and light microscopic observations and morphometric analysis of SAH + Tizanidine administration group and SAH group, and no statistically significant difference between SAH + Tizanidine administration group and control group. CONCLUSION: This study has disclosed that Tizanidine administration before the vasospasm reduces ultrastructural and morphometric vasospastic insult significantly. However, the clinical application of Tizanidine as a protective and therapeutic agent in cerebral vasospasm needs further studies including the employment of clinically more relevant SAH models.

Protective effect of defibrotide on perfusion induced endothelial damage.

In the present study, in vitro effects of Defibrotide (D) on perfusion-induced changes in the morphology of endothelium were investigated by scanning (SEM) and transmission (TEM) electron microscope. Human umbilical cord veins were incubated or perfused with platelet-rich plasma alone (PRP) or platelet-rich plasma with Defibrotide (PRP+D) at 3ml/min or 14ml/min and the changes observed were compared. SEM examination of luminal surfaces demonstrated that perfusion with high flow rates may damage endothelial cells and lead to morphological changes which may be prevented by the presence of Defibrotide in the perfusate. Also, the marked reduction in the number of adhered platelets on luminal surface of veins incubated or perfused with Defibrotide compared to veins treated with platelet-rich plasma only revealed that Defibrotide has anti-thrombotic effects. TEM examination of ruthenium red (RR) stained thin sections of veins demonstrated that perfusion disrupts the glycosaminoglcan (GAG) coat on endothelial cells. But the presence of D in the perfusate preserves the integrity of GAG, indicating further cytoprotective effects of the drug on endothelium.