Non-lethal Hallermann-Streiff syndrome with bone fracture: report of a case

The Hallermann-Streiff syndrome is characterized by bird-like face, micropthalmia, cataracts, micrognathia, beaked nose, abnormal dentition, hypotrichosis, cutaneous atrophy and proportional small stature. We present a 35-day-old patient with the classical signs except cutaneous atrophy, additionally he had a healing fracture at the proximal part of the left radius.     

Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly

Aging is accompanied by a progressive decline in immune function. Studies have shown age-related decreases in the expression and signaling efficiency of Toll-like receptors (TLRs) in monocytes and dendritic cells and dysregulation of macrophage TLR3. Using a multivariable mixed effect model, we report a highly significant increase in TLR5-induced production of IL-8 from monocytes of older individuals (P < 0.0001). Elevated IL-8 is accompanied by increased expression of TLR5, both protein and mRNA, and by increased levels of TLR5-mediated phosphorylation of MAPK p38 and ERK. We noted incomplete activation of NF-κB in response to TLR5 signaling in monocytes of elderly donors, as reflected by the absence of an associated increase in the production of TNF-α. Elevated TLR5 may provide a critical mechanism to enhance immune responsiveness in older individuals.     

Matrix metalloproteinase 9 facilitates West Nile virus entry into the brain

West Nile virus (WNV) is the most-common cause of mosquito-borne encephalitis in the United States. Invasion of the brain by WNV is influenced by viral and host factors, and the molecular mechanism underlying disruption of the blood-brain barrier is likely multifactorial. Here we show that matrix metalloproteinase 9 (MMP9) is involved in WNV entry into the brain by enhancing blood-brain barrier permeability. Murine MMP9 expression was induced in the circulation shortly after WNV infection, and the protein levels remained high even when viremia subsided. In the murine brain, MMP9 expression and its enzymatic activity were upregulated and MMP9 was shown to partly localize to the blood vessels. Interestingly, we also found that cerebrospinal fluid from patients suffering from WNV contained increased MMP9 levels. The peripheral viremia and expression of host cytokines were not altered in MMP9(-/-) mice; however, these animals were protected from lethal WNV challenge. The resistance of MMP9(-/-) mice to WNV infection correlated with an intact blood-brain barrier since immunoglobulin G, Evans blue leakage into brain, and type IV collagen degradation were markedly reduced in the MMP9(-/-) mice compared with their levels in controls. Consistent with this, the brain viral loads, selected inflammatory cytokines, and leukocyte infiltrates were significantly reduced in the MMP9(-/-) mice compared to their levels in wild-type mice. These data suggest that MMP9 plays a role in mediating WNV entry into the central nervous system and that strategies to interrupt this process may influence the course of West Nile encephalitis.     

Anatomical and functional plasticity of pancreatic beta-cells and type 2 diabetes

The most common form of diabetes, type 2 diabetes (T2D) is a major Public Health issue which is receiving a great deal of attention both in industrial and public research, in order to develop new and more effective drugs. The hyperglycaemia of T2D is the result of two interdependent defects : decreased biological efficacy of insulin in target tissues (insulin resistance), and a decreased capacity for beta cells to secrete insulin in response to glucose. Furthermore, hyperglycaemia evolves with time and even with rigorous treatment there is a progressive deterioration of glucose homeostasis. Seventy five percent of DT2 patients are obese and show a perturbed lipid profile. beta-cell plasticity is a unique property of these cells to adapt their number and volume (beta-cell mass) and their function to the increased secretory demand linked to insulin resistance. This is well documented in physiological (pregnancy) as well in pathophysiological conditions (obesity, acromegaly). Although the lack of reliable techniques makes it very difficult to document it in humans, this property is likely altered in DT2, mainly as a consequence of the prolonged exposure of islet cells to high plasma levels of glucose and free fatty acids (gluco-lipotoxicity). The mechanisms by which hyperglycaemia and hyperlipidemia exert their deleterious effects on the beta-cell include the generation of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) and Advanced Glycosylation End Products (AGE). Altogether the prevailing clinical and experimental data urge us to consider that the pathophysiology of DT2 lies, at least in part, the inability of beta-cells to adapt their functional mass to the prevailing insulin demand. This re-evaluation of the pathophysiology of DT2 stimulates the research of new therapeutic approaches aimed at maintaining and/or restoring the functional beta-cell mass by targeting the mechanisms responsible for its decrease.     

Histopathological changes induced by maneb and carbaryl on some tissues of rainbow trout, Oncorhynchus mykiss

Acute toxicity of the pesticides, maneb and carbaryl, to juvenile rainbow trout were evaluated under static-renewal test conditions. Actual concentrations of maneb ranged from 0.10 mg/L to 2.00 mg/L and carbaryl ranged from 0.20 mg/L to 3.90 mg/L. The concentrations of maneb that killed 50% of the rainbow trout (3.27 ± 0.9 g) within 24-h (24-h; LC₅₀), 48-h, 72-h and 96-h were 1.19 ± 0.12, 1.04 ± 0.11, 0.92 ± 0.12 and 0.81 ± 0.14 mg/L (95% confidence limits), respectively. LC₅₀ values of carbaryl for 24-h, 48-h, 72-h and 96-h were 2.52 ± 0.71, 2.16 ± 0.63, 1.71 ± 0.46 and 1.39 ± 0.15 mg/L, respectively. None of the unexposed control fish died and the first fish died 6 h after exposure to maneb (≥1.30 mg/L), and carbaryl (≥2.60 mg/L). Lamellar edema, separation of epithelium from lamellae, lamellar fusion, swelling of the epithelial cells and epithelial cell necrosis were observed on maneb and carbaryl exposed fish. Gills also had scattered areas of focal lamellar hyperplasia. Fish exposed to pesticides had inflammation and focal necrosis in liver, trunk kidney and spleen. Maneb and carbaryl had similar histopathological lesions. In order, the most affected organs were gill, trunk kidney and liver.     

The Turkish delight: a pliable graft for rhinoplasty

In nose surgery, carved or crushed cartilage used as a graft has some disadvantages, chiefly that it may be perceptible through the nasal skin after tissue resolution is complete. To overcome these problems and to obtain a smoother surface, the authors initiated the use of Surgicel-wrapped diced cartilage. This innovative technique has been used by the authors on 2365 patients over the past 10 years: in 165 patients with traumatic nasal deformity, in 350 patients with postrhinoplasty deformity, and in 1850 patients during primary rhinoplasty. The highlights of the surgical procedure include harvested cartilage (septal, alar, conchal, and sometimes costal) cut in pieces of 0.5 to 1 mm using a no. 11 blade. The fine-textured cartilage mass is then wrapped in one layer of Surgicel and moistened with an antibiotic (rifamycin). The graft is then molded into a cylindrical form and inserted under the dorsal nasal skin. In the lateral wall and tip of the nose, some overcorrection is performed depending on the type of deformity. When the mucosal stitching is complete, this graft can be externally molded, like plasticine, under the dorsal skin. In cases of mild-to-moderate nasal depression, septal and conchal cartilages are used in the same manner to augment the nasal dorsum with consistently effective and durable results. In cases with more severe defects of the nose, costal cartilage is necessary to correct both the length of the nose and the projection of the columella. In patients with recurrent deviation of the nasal bridge, this technique provided a simple solution to the problem. After overexcision of the dorsal part of deviated septal cartilage and insertion of Surgicel-wrapped diced cartilage, a straight nose was obtained in all patients with no recurrence (follow-up of 1 to 10 years). The technique also proved to be highly effective in primary rhinoplasties to camouflage bone irregularities after hump removal in patients with thin nasal skin and/or in cases when excessive hump removal was performed. As a complication, in six patients early postoperative swelling was more than usual. In 16 patients, overcorrection was persistent owing to fibrosis, and in 11 patients resorption was excessive beyond the expected amount. A histologic evaluation was possible in 16 patients, 3, 6, and 12 months postoperatively, by removing thin slices of excess cartilage from the dorsum of the nose during touch-up surgery. This graft showed a mosaic-type alignment of graft cartilage with fibrous tissue connection among the fragments. In conclusion, this type of graft is very easy to apply, because a plasticine-like material is obtained that can be molded with the fingers, giving a smooth surface with desirable form and long-lasting results in all cases. The favorable results obtained by this technique have led the authors to use Surgicel-wrapped diced cartilage routinely in all types of rhinoplasty.