Neuronal death in the central nervous system demonstrates a non-fibrin substrate for plasmin

Mice deficient for plasminogen exhibit a variety of pathologies, all of which examined to date are reversed when the animals are also made fibrin(ogen) deficient. These results suggested that the predominant, and perhaps exclusive, physiological role of plasminogen is clearance of fibrin. Plasminogen-deficient mice also display resistance to excitotoxin-induced neurodegeneration, in contrast with wild-type mice, which are sensitive. Based on the genetic interaction between plasminogen and fibrinogen, we investigated whether resistance to neuronal cell death in the plasminogen-deficient mice is dependent on fibrin(ogen). Unexpectedly, mice lacking both plasminogen and fibrinogen are resistant to neurodegeneration to levels comparable to plasminogen-deficient mice. Therefore, plasmin acts on substrates other than fibrin during experimental neuronal degeneration, and may function similarly in other pathological settings in the central nervous system.     

Retinal specificity in eye fragments: investigations on the retinotectal projections of different quarter-eyes in Xenopus laevis

According to Sperry's chemoaffinity hypothesis, the projection of a small eye fragment with a reduced amount of optic fibres should be restricted to that position in the optic tectum corresponding to its own specificity. However, previous investigations on different types of quarter-eyes in Xenopus laevis have revealed that their retinal projection was always restricted to the rostral part of the tectum, no matter what the origin of the remaining retinal quadrant. To get an indication of the state of specificity in such eye fragments, we investigated by electrophysiological and histological methods several features of the retinal projections of temporoventral (TV), naso-ventral (NV) and ventral (V) quarter-eyes which referred to their positional identity. Irrespective of their different origins, the projections were always located in the rostral part of the tectum, the size of the innervated tectal area depending for all fragment types on the size of the quarter-eyes, i.e. number of optic fibres. However, quantitative analyses revealed that with increasing eye size the various fragments expand their projections preferentially into those tectal areas that match their original specificity: TV projection is more concentrated in the rostral tectum, NV eyes expand their projections mainly to the caudal tectum, and V eyes enlarge their projections equally into the medial and caudal tectum. In addition, fibre-tracing experiments with cobaltic lysine showed that, according to the different origins of the quarter-eyes, retinal fibres follow the appropriate branch of the optic tract selectively: fibres of NV and V eyes pass mainly through the medial tract, and most fibres of TV eyes innervate the rostral tectum directly from a central position between the two side branches. All these findings suggest that the different types of quarter-eyes retain their original positional identity. Thus, their rostrally located retinotectal projections are not in register with their retinal specificity. We conclude that in X. laevis local positional markers in the tectum, if present at all, do not influence the development of the retinotectal projection. Instead we suggest a concept of self-sorting of the optic fibres, which can account for the partial innervation of the rostral tectum in different types of quarter-eyes.     

Fat in the intestine as a regulator of appetite--role of CCK

The present review summarizes the appetite-suppressing effects of intestinal fat in the regulation of food intake in humans, with a special focus on the role of cholecystokinin (CCK). Current evidence supports a role for intestinal fat (especially long-chain free fatty acids) acting via the peptide CCK as a physiological satiety pathway. The regulation of satiety is, however, complex and it is not surprising that multiple control systems exist. It is interesting to note that nutrients, such as hydrolysis products of fat in the small intestine, stimulate the release of satiety peptides, such as CCK or PYY, that serve as satiety signals. CCK, released from the gastrointestinal tract by the local action of digested food, exerts various functions: stimulation of gallbladder contraction and exocrine pancreatic secretion, inhibition of gastric emptying, and inhibition of appetite. CCK functions therefore (1) as a positive feedback signal to stimulate digestive processes and (2) as negative feedback signal to limit the amount of food consumed during an individual meal.     

Chronic methamphetamine and its withdrawal modify behavioral and neuroendocrine circadian rhythms

Chronic methamphetamine (MA) administration via the drinking water not only induced hyperactivity, but phase delayed the rat rest-activity cycle under entrained conditions. The minimum and/or maximum of the rhythms in eating, drinking, body weight, core body temperature and plasma/urine corticosterone were delayed. The different phase shifts of peak and trough values can also be a result of modulation in the wave form of the rhythms. The fall, but not the rise, of nocturnal pineal melatonin secretion occurred 4 hours earlier in MA-treated rats than in controls: this pattern was still present 1 week after withdrawal, but no longer after 4 weeks withdrawal. Neither chronic MA nor its withdrawal had any effect on plasma thyrotropin. These patterns after chronic MA intake fall into two groups: those rhythms whose peak and/or trough are delayed and those that are not. We thus interpret chronic MA application as modulating the eating rhythm (though not directly through rhythmic MA levels in the CNS), and that this in turn changes all food-dependent rhythms. In contrast, the circadian rhythms of melatonin and thyrotropin remain independent.     

Cutaneous larva migrans on the scalp: atypical presentation of a common disease

Cutaneous larva migrans is a pruritic dermatitis due to the inoculation of helminths larvae in the skin, and it often occurs in children in tropical and subtropical areas. The authors describe an atypical case of cutaneous larva migrans in a 11 year-old child with scalp involvement, an unusual topography for this lesion.     

The use of HIV post-exposure prophylaxis in forensic medicine following incidents of sexual violence in Hamburg,Germany: a retrospective study

In Hamburg, Germany, the initiation of HIV post-exposure prophylaxis (HIV PEP) in cases of sexual violence is often carried out by forensic medical specialists (FMS) using the city’s unique Hamburg Model. FMS-provided three-day HIV PEP starter packs include a combination of raltegravir and emtricitabine/tenofovir. This study aimed to investigate the practice of offering HIV PEP, reasons for discontinuing treatment, patient compliance, and whether or not potential perpetrators were tested for HIV. We conducted a retrospective study of forensic clinical examinations carried out by the Hamburg Department of Legal Medicine following incidents of sexual violence from 2009 to 2016. One thousand two hundred eighteen incidents of sexual violence were reviewed. In 18% of these cases, HIV PEP was initially prescribed by the FMS. HIV PEP indication depended on the examination occurring within 24 h after the incident, no/unknown condom use, the occurrence of ejaculation, the presence of any injury, and the perpetrator being from population at high risk for HIV. Half of the HIV PEP recipients returned for a reevaluation of the HIV PEP indication by an infectious disease specialist, and just 16% completed the full month of treatment. Only 131 potential perpetrators were tested for HIV, with one found to be HIV positive. No HIV seroconversion was registered among the study sample. Provision of HIV PEP by an FMS after sexual assault ensures appropriate and prompt care for victims. However, patient compliance and completion rates are low. HIV testing of perpetrators must be carried out much more rigorously.     

Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells

Detailed studies of tumor cell-associated procoagulants and fibrinolytic factors have implied that local thrombin generation and fibrin deposition and dissolution may be important in tumor growth and dissemination. To directly determine whether fibrin(ogen) or plasmin(ogen) are determinants of the metastatic potential of circulating tumor cells, this study examined the impact of genetic deficits in each of these key hemostatic factors on the hematogenous pulmonary metastasis of 2 established murine tumors, Lewis lung carcinoma and the B16-BL6 melanoma. In both tumor models, fibrinogen deficiency strongly diminished, but did not prevent, the development of lung metastasis. The quantitative reduction in metastasis in fibrinogen-deficient mice was not due to any appreciable difference in tumor stroma formation or tumor growth. Rather, tumor cell fate studies indicated an important role for fibrin(ogen) in sustained adhesion and survival of tumor cells within the lung. The specific thrombin inhibitor, hirudin, further diminished the metastatic potential of circulating tumor cells in fibrinogen-deficient mice, although the inhibitor had no apparent effect on tumor cell proliferation in vitro. The absence of plasminogen and plasmin-mediated fibrinolysis had no significant impact on hematogenous metastasis. The authors concluded that fibrin(ogen) is a critical determinant of the metastatic potential of circulating tumor cells. Furthermore, thrombin appears to facilitate tumor dissemination through at least one fibrin(ogen)-independent mechanism. These findings suggest that therapeutic strategies focusing on multiple distinct hemostatic factors might be beneficial in the containment of tumor metastasis.     

Assessment of recombinant porcine follicle-stimulating hormone receptor using a novel polyclonal ectodomain antibody

Follicle-stimulating hormone (FSH) receptors (FSHR) are critically involved in mediating the responses of granulosa cells and Sertoli cells to FSH. The dynamic changes in cell surface FSH receptors (FSHR) in response to FSH remain unclear in part because of the heavy reliance on ligand-binding methodologies. This study was designed to determine the molecular and cellular properties of recombinant porcine FSHR using a novel, high-affinity purified polyclonal antibody to the ectodomain of the pFSHR. A full-length porcine FSHR cDNA was cloned and sequenced and recombinant pFSHR protein was stably expressed in a clonal cell line of Chinese hamster ovary cells (pFSHR-CHO). Recombinant receptor was stably expressed in an ovarian cell line with a density similar to that of porcine ovarian cells. A specific polyclonal antibody was generated in chickens to a 100-amino acid fragment of the pFSHR ectodomain. Immunoblotting, immunoprecipitation, indirect immunofluorescence cytochemistry and immunoelectron microscopy were performed using affinity-purified antibody to identify recombinant pFSHR in pFSHR-CHO cells. Immunoblotting of solubilized pFSHR-CHO proteins and immunoprecipitation of pFSHR-CHO protein metabolically labeled with 35S identified a single 74-kDa band in pFSHR-CHO cells; no bands were visualized in mock-transfected CHO cells. Indirect immunofluorescent labeling revealed the presence of pFSHR in pFSHR-CHO cells but not in mock-transfected CHO cells. Immunoelectron microscopy revealed the highest density of pFSHR associated with the plasma membrane and no pFSHR in mock-transfected CHO cells. The chicken anti-pFSHR antibody is a valuable tool for detecting and monitoring of FSHR using a variety of methodologies.