Asprosin improved neuronal survival by suppressing apoptosis and enhancing the activity of the autophagy pathway in the MCAO model in rats.

OBJECTIVE: Cerebral ischemia (CI) is a condition in which metabolic stress increases when blood flow is interrupted in a part of the brain, resulting in oxygen and glucose deprivation. It is known that asprosin (Asp), secreted from adipose tissue during fasting, has an effect on some metabolic processes such as apoptosis, autophagy, and glucose metabolism. This study aimed to explain which of the cell death/survival Asp induces in the CI/reperfusion model. MATERIALS AND METHODS: In the study, 48 male Wistar Albino rats were divided into 6 groups: Sham, CI, Asp+CI, CI+Asp, CI+Asp+3-MA, and Asp+CI+3-MA (n=48). CI was created using the intraluminal filament technique for 60 minutes, autophagy inhibitor 3-MA (15 mg/kg/day) and Asp (1 µg/kg/day) injections were administered 3 days before or 3 days during reperfusion. Beclin-1, ATG5, ATG7, p62, Bcl-2, Bax, active-caspase-3, and active-caspase-9 protein levels from brain tissues were determined by the Western-Blot method. The infarct area was determined by triphenyl tetrazolium chloride (TTC) staining. The Kruskal-Wallis' test was used to compare differences between groups. p<0.05 was considered statistically significant. RESULTS: Compared to the Sham group, the increase in ischemic area and the decrease in Beclin-1, ATG-5, ATG-7, Bcl-2, Bax, active-caspase-3 and active-caspase-9 levels in the CI groups are statistically significant (p<0.05). The increase of Beclin-1, ATG-7, Bcl-2, and Bax levels in the Asp groups is statistically significant compared to the CI group (p<0.05). When Asp+CI groups and CI+Asp groups are compared, an increase in Beclin-1 levels in the Asp+CI group and the increase in Bcl-2, Bax, active-caspase-3/9 and ATG-5 levels in the CI+Asp groups are statistically significant (p<0.05). CONCLUSIONS: Asp has protective and therapeutic effects against CI/R damage. While applying Asp before ischemia activates the autophagy pathway more, applying it after ischemia protects the neuronal death/survival balance by activating the apoptosis pathway more.

The optical characterization of metal-mediated aggregation behaviour of amphiphilic Zn(ii) phthalocyanines.

Ag(+) mediated aggregation behaviour of two different amphiphilic zinc phthalocyanines (Zn-Pcs) (symmetric and asymmetric) has been investigated in solution, at the air-water interface and in Langmuir-Blodgett (LB) films transferred onto glass substrates. A 4 : 1 ([Ag(+)]/[Pc]) complexation was observed for both symmetric and asymmetric Zn-Pcs at high [Ag(+)] concentrations which led to the formation of H-aggregates in solution. At the air-water interface, both symmetric and asymmetric Zn-Pcs showed a tilted, edge-on orientation in columnar stacks. Addition of Ag(+) to the subphase enhanced the order in the monolayers. LB films on glass substrates showed a split Q-band indicating the presence of "herring-bone" type aggregation consisting of both H- and J-aggregates. For LB films deposited from a Ag(+) containing subphase, a shoulder appeared in the absorption spectra at longer wavelengths which indicates that the fraction of J-aggregates was enhanced by Ag(+) in LB films. The molecular orientation in LB films was investigated by polarized absorption spectroscopy and a tilt angle was calculated to be 49° with the substrate normal for symmetric and 74.6° for the asymmetric Zn-Pc. The presence of Ag(+) cations in the subphase decreased the tilt angles slightly by 4-5°. These results indicate that Ag(+) induced the aggregation of Zn-Pcs and acted as a linker between Pc molecules in the ultrathin films of both symmetric and asymmetric Zn-Pcs. These results are important in inducing J-aggregates for the fabrication of molecular devices based on phthalocyanine thin films.

Fatty liver disease in an autopsy series of children and adolescents.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents. Obesity is a major risk factor for NAFLD; however, it has been shown that NAFLD is not rare in non-obese adults. The aim of this study was to determine the prevalence of NAFLD in obese and non-obese children and adolescents. METHODS: The medical records of 340 subjects (aged 2-20 years) in whom autopsy was performed were retrospectively reviewed. Of those, 10 subjects were excluded due to insufficient data. The remaining 330 subjects were included in the study, of whom 264 were normal weight and 66 were obese. All liver biopsy sections were evaluated by two pathologists in a blinded fashion. RESULTS: The prevalence of fatty liver was 6% among all the subjects and was higher in the overweight group than in the normal-weight group (10.6% vs 4.9%; p<0.001). The prevalence of NAFLD increased concomitant with age. There was no significant difference between sexes in cases with NAFLD. Simple steatosis was detected in 7 subjects. Steatohepatitis was determined as type 1 in 5 subjects, type 2 in 7 subjects, and as overlap in 1 subject. CONCLUSIONS: This study demonstrated that NAFLD is an important public health problem not only in obese but also in non-obese children and adolescents. This suggests that whereas obesity may be a risk factor, other pathogenic factors may exist that could contribute to the NAFLD.

Low transforming growth factor-beta1 serum levels in idiopathic male osteoporosis.

INTRODUCTION: Although the etiology of osteoporosis is different between men and women, the underlying pathophysiological mechanism is similar, namely an absolute or relative increase in bone resorption, leading to progressive bone loss. Transforming growth factor (TGF)-beta1 is a growth factor in human bone, which is produced by osteoblasts, and which has various effects on osteoclasts and osteoblasts. The aim of our study was to determine serum TGF-beta1 levels in male patients with idiopathic osteoporosis. METHODS: Twenty five males with idiopathic osteoporosis and 25 age-matched controls were studied. Osteoporosis was defined by a T score of <-2.5 in the lumbar spine or at the femoral neck. We measured levels of TGF-beta1, estradiol, total and bioactive testosterone. Various markers of bone remodeling were also measured. RESULTS: TGF-beta1 was significantly lower in osteoporotic patients than in controls (3.706 ng/dl, 25-75 percentiles: 2.81-5.33 vs 8.659 ng/dl, 25-75 percentiles: 4.837-11.835; p=0.000). Moreover, TGF-beta1 levels were positively correlated with bone mineral density (BMD) at the femoral neck (r=0.439, p=0.028), and at the lumbar spine (r=0.41, p=0.042). No correlation was found between serum estradiol, testosterone and TGF-beta1 levels. DISCUSSION: Serum TGF-beta1 levels are depressed in osteoporotic men and are positively correlated with hip and spine BMD. The results of our study suggest that TGF-beta1 may play a role in the pathogenesis of idiopathic male osteoporosis.

Nerve regeneration through an epineurial sheath: its functional aspect compared with nerve and vein grafts.

Although nerve graft is still the only reliable choice in repair of defects in peripheral nerve structure, it has the disadvantage of donor nerve morbidity and of sometimes being unavailable. It has long been researched in alternate nerve grafts with other materials. Studies have shown that nerves could regenerate across short nerve gaps through various conduits, such as veins, pseudosheaths, and bioabsorbable tubes. Despite encouraging studies, their functional results remain unclear. The present study used 40 rats, in which nerve grafts, vein grafts, and epineurial tubes were placed into 1-cm gaps in sciatic nerves created by resection. In one group, sciatic nerves were denuded of the surrounding epineurium, to assess the possible morbidity caused by epineurial sheath technique. At 2, 4, 8, 12, 20, and 28 weeks, functional assessment of nerve regeneration was performed using walking track analysis. The number of myelinated fibers and fiber diameters was measured and electron microscopic evaluation performed. Functionally, the index values were very close to each other in nerve graft and epineurial sheath groups. Morphometric analysis showed significance between the groups. The result of denuded sciatic nerve group was the same as the base track values. It was concluded that the ready availability of epineurial sheath as a conduit to span short nerve gaps could eliminate the morbidity associated with nerve graft harvest and capitalize on the potential benefits of neurotrophism in directing nerve regeneration.

Wiping away debris between passes during laser surgery: is it really efficient or causing complications?

Although carbon dioxide laser skin resurfacing offers a controlled and predictive tissue ablation, it is not completely without complications, such as cobblestone-like appearance or scar formation. It has been supposed that these were the results of thermal loading on overlapped areas. In order to obtain a smoother surface, an experimental study dealing with the effect of wiping procedure between the sessions was carried out. Laser beams were applied in two sessions to the backs of 20 rats. Between the sessions, the debris was wiped away in half and left unwiped in the others. Despite a statistically higher ablation rate in the wiped group, its surface irregularity was statistically significant when compared to unwiped group. It is supposed that the amount of debris left on the surface has the regulatory role in laser application. Because laser beams can be absorbed more by untreated skipped areas and less by overlapped sites, the second pass can ensure a smoother surface. Considering both benefits and disadvantages, it is concluded that wiping vaporized debris every two passes is the most reliable laser treatment modality.

Increased levels of tissue factor pathway inhibitor may reflect disease activity and play a role in thrombotic tendency in Behçet's disease.

Tissue factor pathway inhibitor (TFPI) is a Kunitz-type proteinase inhibitor that has a crucial role in haemostasis and is primarily synthesized in the vascular endothelium. We investigated plasma total TFPI, antiphospholipid antibodies, and some other coagulation and fibrinolytic system parameters in 30 patients with Behçet's disease and 15 controls by the enzyme-linked immunosorbent assay method. TFPI levels were significantly higher in the Behçet's group (119 +/- 57.5 ng/ml) compared with the control group (74.8 +/- 31.5) (P < 0.009). We also noted a statistical significance in TFPI levels between patients with active disease (n:16) (139 +/- 55) and patients without activation (n:14) (96 +/- 53) (P < 0.03), whereas inactive patients lacked any significance when compared with the control group (P < 0.29). Other parameters disclosed no statistical significance between patients and control group except for elevated fibrinogen and plasminogen activator inhibitor-1 levels in the patient group (P < 0.003). Increased levels of TFPI may reflect a defensive mechanism like in other diseases characterized by thrombotic tendency and represent a parameter of disease activity.

Replantation of an avulsive amputation of a foot after recovering the foot from the sea.

A foot avulsion case, with the dismembered body part submerged in sea water for 1 hour, is presented. This report is unique in that it is the first to document the reattachment of a body part that had been submerged in sea water. It was not known how salt-water exposure would affect wound management. Differences in osmolarity and bacterial flora between the sea water and foot tissues have not caused any problems, and the patient has not suffered any vascular or infectious complications after replantation. Neurotization of the plantar surface by the tibial nerve, which was stripped off during amputation and replaced in its original traces, was the most critical part of convalescence. After management of such an interesting case, we conclude that exposure to sea water of the dismembered part should not be a contraindication for replantation surgery.

Nerve regeneration through side-to-side neurorrhaphy sites in a rat model: a new concept in peripheral nerve surgery.

Despite great improvement and refinements in nerve repair techniques, there were still problems in repair of peripheral nerve injuries for which proximal stumps were not available. In these circumstances for which classic end-to-end neurorrhaphy was impossible, new treatment modalities, benefiting by an adjacent healthy nerve, have been under investigation to overcome this problem. Therefore, end-to-side nerve repair with its modifications came to view and axonal passages through this site were shown. Moreover, the results were unsatisfactory or necessitating sacrifice of another healthy nerve. Three groups, containing 10 rats each, were included in the study. First was the control group, with end-to-end repair of the peroneal nerve. Second was the end-to-side repair group, in which the distal stump of the peroneal nerve trunk was anastomosed to the lateral side of the tibial nerve. The third was the side-to-side repair group. In this technique, 1-mm diameter epineural windows, both from peroneal and tibial nerve trunks facing each other, were removed and side-to-side neurorrhaphy was performed. After 3 weeks, as the second step, the peroneal nerve was sectioned proximally. At 2, 4, 8, 12, 20, and 28 weeks, functional assessment of nerve regeneration was performed by using walking track analysis. The number of myelinated fibers and fiber diameters were measured and an electron microscopic evaluation was carried out. Statistically, both in morphometric and gait analysis, the differences in values between the groups were significant in favor of the control group, followed by the side-to-side group. The study showed that axonal passage was possible with side-to-side technique and the functional results were satisfactory and superior to the end-to-side technique. Continuous supply of neurotrophic factors from their target cells was the probable cause of superior functional return in side-to-side repair, because both joining nerves were intact and healthy during the anastomosis procedure and after 3 weeks. It was concluded that this technique could be indicated in salvage of nerves in cases for which any intermediate segments would be removed, as in tumor ablation surgery, harvesting of nerve grafts, or both.

"Tandir": an old and well known cause of burn injury in the Middle East.

Analysis of an unusual cause of burn injury together with assessment of long-term end results was carried out. The 'tandir' is a kind of oven buried underground and resembles a big hole full of embers and surrounded with sheet iron. Most of the burn victims were children. 68 major burn cases have been admitted to our units in a 3 year period, 32 (47%) of them due to a 'tandir'. In most of the cases burn injuries included the head and both hands as a result of the specific characteristics of the 'tandir'.

MHC class I antigen expression in patients with IDDM and their siblings.

MHC class I antigen expression was found to be low on the lymphocytes of patients with insulin dependent diabetes mellitus (IDDM). Thus, it has been proposed that the defective expression of MHC antigens could lead to faulty immunological responses with the eventual destruction of the pancreatic beta cells. The objective in this study was to compare MHC antigen expression in IDDM patients and their presently healthy siblings. Nineteen children (mean age 10.8 +/- 3.9 years) with diabetes and their 25 siblings (mean age 10.7 +/- 4.6 years) were enrolled in the study. Peripheral blood lymphocytes isolated from venous blood samples were incubated with FITC conjugated monoclonal antibody W6/32. The amount of antibody binding by cell surface MHC class I antigens was assessed by flow cytometry. MHC class I molecule expression did not differ significantly among IDDM patients and their siblings. It was concluded that MHC class I antigen expression did not appear to be indicative of a susceptibility to develop autoimmune diabetes.

Prevention of painful neuromas by epineural ligatures, flaps and grafts.

Neuroma formation at the proximal end of a divided nerve is a common problem in peripheral nerve surgery. Forty-eight nerve endings in 23 patients with traumatic or post-elective surgery amputation stumps were capped with either an epineural ligature, epineural flaps or an epineural graft. Each technique was used on 16 nerve endings. After at least 6 months follow-up, pain at the nerve endings was assessed by tapping the treatment sites and asking the patients to score their pain on a visual analogue scale (VAS) from 0 to 10. The mean VAS scores were 5.18 for epineural ligatures, 4.25 for epineural flaps and 2.06 for epineural grafts. Epineural grafts were significantly more effective in preventing neuroma pain (ANOVA: F = 11.4, P < 0.05).

Rationale for early tangential excision and grafting in burn patients.

Early excision and grafting of the burn wound in the first 9 days remain the keys to survival for patients with major burn injuries. In the last 7-year-period, 54 major burn cases were treated in our burn facility, the only Burn Center in Istanbul. Early excision and grafting were performed to 32 of them, admitted in the first week. Others were admitted later and managed conservatively. Their follow-up results in terms of mortality and morbidity rates were compared. In addition to improvement in the prognosis, early excision and grafting procedures decreased the duration of hospitalization and cost of burn treatment.

Lack of NK cells in lupus patients with renal involvement.

We have previously shown that patients with SLE have significantly lower percentages and absolute numbers of NK(CD3-/CD16+56) cells in their peripheral blood compared with normals. Patients with active disease had very low levels of NK cells and the reduction was also associated with patients who had renal involvement. We have now performed a serial study immunophenotyping 11 patients with SLE and renal involvement using dual colour immunofluorescence and flow cytometry. Patients were tested every three months on an average of three occasions. As a control, nine SLE patients without renal involvement were immunophenotyped for similar intervals; 11 normal controls were also tested. Major lymphocyte subsets (T, B and NK) remained very stable during serial bleeds. However, the NK cell populations were decreased significantly in patients with renal involvement both as percentages (5 +/- 6 vs 9 +/- 5, P < 0.0001) and absolute counts (75 +/- 108 vs 109 +/- 52, P < 0.001) in comparison to non-renal patients. Analysis of disease activity using BILAG score showed an inverse correlation between renal system activity and percentage and absolute number of NK cells (P < 0.002 and 0.01, respectively). In this study we have also analysed a CD8 T cell subset which we have not studied before. We have found a significantly increased percentage of CD38+CD8+ T cells(activated CD8 subset) in patients with SLE in comparison to normal controls. We did not find any association with the CD38+CD8+ T cells and disease activity as measured by BILAG or renal involvement. NK cells are important factors in immunity against virus infections and tumour cells. CD38+CD8+T cells are increased in viral infections. We speculate that the lack of NK cells in SLE patients might have an association with increased CD38 expression.