Effects of ischemic phrenic nerve root ganglion injury on respiratory disturbances in subarachnoid hemorrhage: an experimental study

Introduction

Phrenic nerves have important roles on the management of respiration rhythm. Diaphragm paralysis is possible in phrenic nerve roots ischemia in subarachnoid hemorrhage (SAH). We examined whether there is a relationship between phrenic nerve root ischemia and respiratory disturbances in SAH.

Material and methods

This study was conducted on 5 healthy control and 14 rabbits with experimentally induced SAH by injecting autologous blood into their cisterna magna. Animals were followed up via monitors for detecting the heart and respiration rhythms for 20 days and then decapitaed by humanely. Normal and degenerated neuron densities of phrenic nerve root at the level of C4 dorsal root ganglia (C4DRG) were estimated by Stereological methods. Between the mean numerical density of degenerated neurons of C4DRG and respiratory rate/minute of groups were compared statistically.

Results

Phrenic nerve roots, artery and diaphragm muscles degeneration was detected in respiratory arrest developed animals. The mean neuronal density of C4DRG was 13272 ±1201/mm3 with a mean respiration rate of 23 ±4/min in the control group. The mean degenerated neuron density was 2.240 ±450/mm³ and respiration rhythm was 31 ±6/min in survivors. But, the mean degenerated neuron density was 5850 ±650/mm³ and mean respiration rhythm was 34 ±7/min in respiratory arrest developed animals (n = 7). A linear relationship was noticed between the degenerated neuron density of C4DRG and respiraton rate (r = –0.758; p < 0.001).

Conclusions

Phrenic nerve root ischemia may be an important factor in respiration rhythms deteriorations in SAH which has not been mentioned in the literature.     

Alveolar Bone Loss Associated With Age‐Related Macular Degeneration in Males

Background : The aim of this study is to examine the relationship of selected systemic and oral health parameters and the salivary presence of six periodontal pathogens to age‐related macular degeneration (AMD). Methods: The present cross‐sectional study includes data on 1,751 individuals (≥30 years old). General health information was obtained by questionnaires and interviews, including self‐reported diagnosis of AMD, as well as by the general and oral health examination, including panoramic radiography and laboratory analyses. Fifty‐four individuals with degenerative fundus changes formed the AMD group, and the other 1,697 formed the non‐AMD group. Pearson χ² and analysis of variance tests were used for comparisons of categorical parameters and continuous parameters between the participant groups, respectively. A logistic regression analysis was performed to study the association of AMD with alveolar bone loss and the number of teeth by controlling for age, diabetic status, systolic blood pressure, education, and smoking, and also for the carriage of salivary bacteria. Results: Advanced age, systolic blood pressure, and diabetes were associated with AMD (P <0.001), whereas the carriage rates of the examined periodontal pathogens were not. In the whole study population, the participants with AMD had fewer teeth (P <0.001) and more alveolar bone loss (P = 0.004) compared with non‐AMD participants. In a logistic regression model adjusted for age, smoking, and diabetes, alveolar bone loss was associated with AMD in males with an odds ratio of 4.3 (95% confidence interval = 1.3 to 14.6, P = 0.013). Conclusion: In this population‐based health survey, alveolar bone loss is independently associated with AMD in males.     

PKC-β exacerbates in vitro brain barrier damage in hyperglycemic settings via regulation of RhoA/Rho-kinase/MLC2 pathway

Stroke patients with hyperglycemia (HG) develop higher volumes of brain edema emerging from disruption of blood–brain barrier (BBB). This study explored whether inductions of protein kinase C-β (PKC-β) and RhoA/Rho-kinase/myosin-regulatory light chain-2 (MLC2) pathway may account for HG-induced barrier damage using an in vitro model of human BBB comprising human brain microvascular endothelial cells (HBMEC) and astrocytes. Hyperglycemia (25 mmol/L D-glucose) markedly increased RhoA/Rho-kinase protein expressions (in-cell westerns), MLC2 phosphorylation (immunoblotting), and PKC-β (PepTag assay) and RhoA (Rhotekin-binding assay) activities in HBMEC while concurrently reducing the expression of tight junction protein occludin. Hyperglycemia-evoked in vitro barrier dysfunction, confirmed by decreases in transendothelial electrical resistance and concomitant increases in paracellular flux of Evan''s blue-labeled albumin, was accompanied by malformations of actin cytoskeleton and tight junctions. Suppression of RhoA and Rho-kinase activities by anti-RhoA immunoglobulin G (IgG) electroporation and Y-27632, respectively prevented morphologic changes and restored plasma membrane localization of occludin. Normalization of glucose levels and silencing PKC-β activity neutralized the effects of HG on occludin and RhoA/Rho-kinase/MLC2 expression, localization, and activity and consequently improved in vitro barrier integrity and function. These results suggest that HG-induced exacerbation of the BBB breakdown after an ischemic stroke is mediated in large part by activation of PKC-β.     

Increased Density of Demodex folliculorum Mites in Pregnancies with Gestational Diabetes

Objective

To investigate the presence of Demodex in patients with gestational diabetes and the impact of glucose regulation on Demodex density in gestational diabetes.

Subjects and Methods

The study population consisted of 33 patients with gestational diabetes and 30 pregnant women without gestational diabetes (control group). The age, parity, gestational age, and BMI of the study group were recorded and the patients were divided into 2 groups, i.e. those with regulated and unregulated glucose levels, according to their postprandial 1st- and 2nd-hour glucose values. A standardized skin surface biopsy method was used to determine if patients had Demodex folliculorum infestation (>5 mites/cm² of skin).

Results

Patients with gestational diabetes had a statistically significantly higher Demodex density compared to the control group (24.2 vs. 3.3%; p < 0.001). Furthermore, a significantly higher proportion of gestational diabetes patients with unregulated glucose levels had a higher Demodex density compared to those in the regulated subgroup (6/19 vs. 2/14; p = 0.001).

Conclusion

Our study revealed that the Demodex density was increased in gestational diabetes patients. Further, poor glucose regulation could be the mechanism responsible for the increased Demodex density in gestational diabetes patients with unregulated glucose levels compared to those with regulated glucose levels.Key Words: Demodex folliculorum, Gestational diabetes, Pregnancy     

A novel organotypic dento-epithelial culture model: effect of Fusobacterium nucleatum biofilm on B-defensin-2, -3, and LL-37 expression

Background: In the present study, the expression and localization of three epithelial peptides (human β‐defensin [hBD]‐2 and ‐3, and cathelicidin [LL‐37]) are studied in an organotypic dento‐epithelial (OD‐E) model exposed to Fusobacterium nucleatum (Fn) biofilm. Methods: Biofilm of Fn ATCC 25586 or AHN 9508 were produced by culturing each strain on semipermeable membranes. The OD‐E model was constructed by seeding keratinocytes on fibroblast‐containing collagen gels and by placing dentin pieces on the top. A 3‐day‐old biofilm was placed on the top of the OD‐E and the coculture was incubated for 5 hours or 24 hours. Production of epithelial antimicrobial peptides was determined immunohistochemically. Results: After 5 hours of incubation, the biofilm of each Fn strain stimulated expression of hBD‐2 and ‐3. hBD‐2 was localized on superficial layers and hBD‐3 on basal cell layers of the epithelium and dento‐epithelial junctions, whereas LL‐37 was only weakly expressed. After 24 hours, hBD‐2 expression was extended toward basal cell layers of the epithelium. In contrast, hBD‐3 expression extended toward superficial layers of the epithelium. In the case of Fn AHN 9508 biofilm, LL‐37 was localized in the cell layers of the dento‐epithelial junction. Conclusion: In our OD‐E model, epithelial antimicrobial peptide responses to Fn biofilms have distinct regulation and localization characteristics, resembling those known to occur in the gingival epithelium in vivo.     

Continuous infusion of midazolam in the treatment of refractory generalized convulsive status epilepticus

We studied the efficacy and safety of midazolam given as a continuous infusion in the treatment of refractory generalized convulsive status epilepticus (RGCSE). We carried out a prospective, open study, in 19 patients (11 men) with RGCSE in the intensive care unit at Firat Medical Center in Elazig. When intravenous administration of 0.3 mg/kg diazepam (three times at 5-min intervals), 20 mg/kg phenytoin, and 20 mg/kg phenobarbital failed to bring the episode under control, patients were administered an intravenous bolus of midazolam (200 μg/kg) followed by a continuous infusion at 1 μg/kg min. The dose was increased by 1 μg/kg min every 15 min until the episode of seizure was brought under control. The time from beginning of treatment to control of seizures, infusion rate, and side-effects were monitored. The mean age of the patients was 40.4 years (range 16–87 years). The clinical etiology of RGCSE was idiopathic epilepsy (6 cases), anoxicischemic cerebral insult due to cardiac arrest (3), viral encephalitis (2), intrahemispheric hematoma due to hemorrhagic stroke (1), cerebral infarct due to ischemic stroke (1), pituitary adenoma (1), post-traumatic epilepsy (1), renal failure (1), tuberculous meningitis (1), and unknown (2). In eighteen (94.7%) patients, seizures were completely controlled in a mean time of 45 min (range, 5–120 min) at a mean infusion rate of 8 μg/kg min (range, 3–21 μg/kg min). In one patient seizures did not stop. Midazolam administration did not cause any significant change in blood pressure, heart rate, oxygen saturation, or respiratory status. The mean time to full consciousness for patients after stopping the infusion was 1.6 hours (range, 2.0–8.5 hours). The mean infusion duration of midazolam was 14.5 hours (range, 12–25 hours). Midazolam is an effective and safe drug to control RGCSE, and may represent a substantial improvement over current therapeutic approaches such as pentobarbital anesthesia. Received: 15 December 2001 / Accepted in revised form: 10 July 2002 Correspondence to B. Müngen