Quinazoline-based tricyclic compounds that regulate programmed cell death, induce neuronal differentiation, and are curative in animal models for excitotoxicity and hereditary brain disease.

Expanding on a quinazoline scaffold, we developed tricyclic compounds with biological activity. These compounds bind to the 18 kDa translocator protein (TSPO) and protect U118MG (glioblastoma cell line of glial origin) cells from glutamate-induced cell death. Fascinating, they can induce neuronal differentiation of PC12 cells (cell line of pheochromocytoma origin with neuronal characteristics) known to display neuronal characteristics, including outgrowth of neurites, tubulin expression, and NeuN (antigen known as 'neuronal nuclei', also known as Rbfox3) expression. As part of the neurodifferentiation process, they can amplify cell death induced by glutamate. Interestingly, the compound 2-phenylquinazolin-4-yl dimethylcarbamate (MGV-1) can induce expansive neurite sprouting on its own and also in synergy with nerve growth factor and with glutamate. Glycine is not required, indicating that N-methyl-D-aspartate receptors are not involved in this activity. These diverse effects on cells of glial origin and on cells with neuronal characteristics induced in culture by this one compound, MGV-1, as reported in this article, mimic the diverse events that take place during embryonic development of the brain (maintenance of glial integrity, differentiation of progenitor cells to mature neurons, and weeding out of non-differentiating progenitor cells). Such mechanisms are also important for protective, curative, and restorative processes that occur during and after brain injury and brain disease. Indeed, we found in a rat model of systemic kainic acid injection that MGV-1 can prevent seizures, counteract the process of ongoing brain damage, including edema, and restore behavior defects to normal patterns. Furthermore, in the R6-2 (transgenic mouse model for Huntington disease; Strain name: B6CBA-Tg(HDexon1)62Gpb/3J) transgenic mouse model for Huntington disease, derivatives of MGV-1 can increase lifespan by >20% and reduce incidence of abnormal movements. Also in vitro, these derivatives were more effective than MGV-1.

A study investigating the association between compulsive buying with measures of anxiety and obsessive-compulsive behavior among internet shoppers.

BACKGROUND: Compulsive buying is a chronic, repetitive behavior that becomes a primary response to negative events and feelings. Compulsive buyers are obsessed by buying and their behavior occurs in response to negative emotions and results in a decrease in the intensity of negative emotions. Euphoria or relief from negative emotions is the most common consequence of compulsive buying. A large number of studies have investigated the association between compulsive buying and anxiety, and some studies have used the Spielberger trait-state anxiety inventory. PROCEDURE: Compulsive buying, state and trait anxiety and general obsessive-compulsive measures were assessed among 120 habitual internet shoppers (2+ times a week, 70 men and 50 women). RESULTS: Results showed that Edwards Compulsive Buying scale measures were associated with Spielberger trait and not state anxiety measures. Spielberger Trait anxiety measures were also correlated with measures of Yale-Brown Obsessive-Compulsive scale (Y-Bocs). Finally, there were no sex differences in this sample. CONCLUSIONS: The results of this study support existing evidence for an association between compulsive buying and anxiety and they will be discussed in view of current research on comorbidity of behavioural addiction.

Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model.

Antidepressant medication constitutes the first line pharmacological treatment for posttraumatic stress disorder (PTSD), however, because many patients display no beneficial drug effects it has been suggested that combinations of antidepressants with additional drugs may be necessary. The defining symptoms of PTSD include re-experiencing, avoidance and hyperarousal. In addition, PTSD patients were shown to become easily distracted and often suffer from poor concentration together with indications of comorbidity with attention-deficit hyperactivity disorder (ADHD). Methylphenidate (MPH) is the most common and effective drug treatment for ADHD, thus we aimed to investigate the effects of MPH treatment, by itself or in combination with the antidepressants fluoxetine (FLU) or desipramine (DES). We modified an animal model of PTSD by exposing rats to chronic stress and evaluating the subsequent development of behavioral PTSD-like symptoms, as well as the effects on proinflammatory cytokines, which were implicated in PTSD. We report that while FLU or DES had a beneficial effect on avoidance and hyperarousal symptoms, MPH improved all three symptoms. Moreover, the combination of MPH with DES produced the most dramatic beneficial effects. Serum levels of interleukin-1ß (IL-1ß) and IL-6 were elevated in the PTSD-like group compared with the control group, and were decreased by MPH, FLU, DES or the combination drug treatments, with the combination of DES+MPH producing the most complete rescue of the inflammatory response. Considering the versatile symptoms of PTSD, our results suggest a new combined treatment for PTSD comprising the antidepressant DES and the psychostimulant MPH.

Plant-derived nanoparticle treatment with cocc 30c ameliorates attention and motor abilities in sleep-deprived rats.

Sleep is an essential physiological process that underlies crucial cognitive functions as well as emotional reactivity. Thus, sleep deprivation (SD) may exert various deleterious effects. In this study, we aimed to examine the adverse behavioral and hormonal effects of SD and a potential treatment with Plant-derived nanoparticle treatment - cocc 30c. The study was a 4-arm trial with randomization and double-blinding of verum and placebo treatments. SD was induced by using the Multiple Platform Method for 48 h. The effects of SD were evaluated behaviorally (pre-pulse inhibition (PPI), startle response and rotor-rod) at baseline as well as at 6, 12, 24h, and 14 days post deprivation. cocc 30c treatment was administrated Per Os every three hours starting immediately after baseline tests and for a period of 24h. On day 14, blood samples were taken and serum levels of corticosterone, testosterone, serotonin and leptin were tested. We found that cocc 30c improved PPI 12 and 24h post deprivation, likewise, cocc 30c improved motor learning. On day 14 SD led to increased startle response that was ameliorated by cocc 30c. Likewise, SD led to increased levels of corticosterone and serotonin while decreasing testosterone and leptin. Interestingly, cocc 30c treatment has moderated these hormonal alterations. We conclude that the treatment with cocc 30c recovers both short-term behavioral and the long-term hormonal modulations following SD.

Safety and efficacy of 188-rhenium-labeled antibody to melanin in patients with metastatic melanoma.

There is a need for effective "broad spectrum" therapies for metastatic melanoma which would be suitable for all patients. The objectives of Phase Ia/Ib studies were to evaluate the safety, pharmacokinetics, dosimetry, and antitumor activity of (188)Re-6D2, a 188-Rhenium-labeled antibody to melanin. Stage IIIC/IV metastatic melanoma (MM) patients who failed standard therapies were enrolled in both studies. In Phase Ia, 10 mCi (188)Re-6D2 were given while unlabeled antibody preload was escalated. In Phase Ib, the dose of (188)Re-6D2 was escalated to 54 mCi. SPECT/CT revealed (188)Re-6D2 uptake in melanoma metastases. The mean effective half-life of (188)Re-6D2 was 12.4 h. Transient HAMA was observed in 9 patients. Six patients met the RECIST criteria for stable disease at 6 weeks. Two patients had durable disease stabilization for 14 weeks and one for 22 weeks. Median overall survival was 13 months with no dose-limiting toxicities. The data demonstrate that (188)Re-6D2 was well tolerated, localized in melanoma metastases, and had antitumor activity, thus warranting its further investigation in patients with metastatic melanoma.

Traumatic avulsion of kidney into the chest through a ruptured diaphragm in a boy.

This report presents a case of a teenage patient who survived following severe blunt trauma with complete avulsion of the right kidney into the chest through a ruptured diaphragm. The combination of kidney avulsion into the chest is extremely rare. Only three similar cases have been reported in the English literature to date (1-3).

[Spermatic cord hematoma simulating torsion of testis in Henoch-Schönlein syndrome].

Henoch-Schönlein syndrome (HSS) is a systemic disease of young children characterized by colicky pain, with melena, vomiting and damage to the joints, kidneys and other organs. Surgical problems involving the gastrointestinal tract include bleeding, intussusception and perforation. Uncommon complications, caused by bleeding into brain tissue and into the scalp, muscles, chest and scrotum, are real challenges for the physician. Spermatic cord hematoma is a rare complication of HSS. Other complications of HSS mentioned in the literature which affect the male genital system include edema of the spermatic cord or testis, epididymitis, orchitis, bleeding, Morgagni cyst, or hematoma surrounding the testis. Considering the low incidence of testicular torsion in HSS, we believe that when a patient with HSS develops acute testicular pain, noninvasive diagnostic procedures such as Doppler, ultrasound and radioisotope scans should be performed in the hope of avoiding unnecessary surgical interventions. A 2-year-old boy with HSS in whom torsion of the testis developed is reported.

Acute embolic bilateral renal artery occlusions in an elderly patient--case report: importance of early diagnosis.

Acute bilateral renal artery occlusion by emboli is a rare event and diagnosis is very often delayed. There is a high mortality rate because of anuria and controversy exists concerning an appropriate therapeutic regimen. We present the case of an elderly patient with bilateral artery occlusion, treated conservatively with anticoagulants, fibrinolytic agents and dialysis, and a review of the pertinent literature.