Cutaneous leishmaniasis: Clinical report of two cases and review of the recent literature

With 1–1.5 million cases reported every year cutaneous leishmaniasis represents an increasing health problem. The course of cutaneous leishmaniasis varies from a single self‐healing ulcer to a persistent ulcer or progressive mucosal disease with nasopharyngeal destruction. An enormous array of topical and systemic treatment modalities has been endorsed. The response to treatment depends on the species of parasite as well as the host's immunological and genetic status. Species‐specific treatment guidelines based on evidence from controlled studies are highly desirable. We present two cases of cutaneous leishmaniasis, one in a child and one during pregnancy, reviewing various diagnostic and therapeutic measures with special attention to problems in young and pregnant patients.     

Incretin mimetics as a novel therapeutic option for hepatic steatosis.

BACKGROUND: Fat accumulation in the liver or non-alcoholic fatty liver disease (NAFLD) is regarded as a key pathogenic factor and component of the metabolic syndrome. It was reported that administration of the incretin mimetic exenatide reversed hepatic steatosis in an obese mouse model. We had the opportunity to study the effect of additional exenatide administration on liver fat content in a patient with type 2 diabetes. CASE REPORT: A 59-year-old male with poorly controlled type 2 diabetes was treated with exenatide in addition to metformin monotherapy. Following 44 weeks of exenatide therapy, mean the liver fat measured by liver spectroscopy declined from 15.8% to 4.3%. This dramatic decrease in liver fat was accompanied by significant beneficial changes in several cardiovascular disease risk factors and improvement of all liver enzymes, in particular alanine aminotransferase, the most important marker of liver steatosis. CONCLUSION: This case report suggests that the incretin mimetic exenatide decreases hepatic fat accumulation and may play a role in the future treatment of NAFLD, and the associated insulin resistance and cardiovascular risk factors in an ever-growing high-risk population.     

Development of tyrosine hydroxylase-, dopamine- and dopamine β-hydroxylase-immunoreactive neurons in a teleost, the three-spined stickleback

The development of catecholaminergic neuronal systems in the brain of a teleost, the three-spined stickleback, was studied through embryonic to early larval stages by immunocytochemistry using specific antibodies against dopamine, tyrosine hydroxylase and dopamine β-hydroxylase. By analysing the spatiotemporal patterns of development for the catecholaminergic nuclei, possible homologies with nuclei in amniote brains have been identified.

The noradrenergic neurons in the isthmus region of the rostral rhombencephalon originate in the same manner as the A4–A7 + subcoeruleus group in mammals. Their developmental characteristics show the largest similarities with the subcoeruleus group of birds and mammals, although some features are shared with developing A6 (locus coeruleus) neurons.

Catecholaminergic neurons never appear during development in the ventral mesencephalon of the three-spined stickleback. A group of large dopaminergic neurons that accompany the cerebrospinal fluid (CSF)-contacting neurons follows the border between the hypothalamus and the ventral thalamus into the caudal hypothalamus, where they are continuous with the dopaminergic neurons in the posterior tuberculum. They are thus topologically comparable with the dopaminergic neurons of the zona incerta in mammals.

The dopaminergic CSF-contacting neurons that line the median, lateral and posterior recesses of the third ventricle do not contain tyrosine hydroxylase-immunoreactivity at any developmental stage. This indicates that they take up and accumulate exogenous dopamine or -dihydroxyphenylalanine, and do not synthesize dopamine from tyrosine at any developmental stage. Tyrosine hydroxylase-immunoreactive neurons appear in the pineal organ on the day of hatching (120 h post-fertilization). They were still observed in 240-h-old larvae, but are absent in the pineal organ of adult sticklebacks.

The initial appearance and subsequent differentiation of catecholaminergic neurons in the stickle-back embryo follow essentially the same spatial and temporal pattern as in amphibian, avian and mammalian embryos. This observation supports the hypothesis that morphologically, topologically and chemically similar monoaminergic neurons in different vertebrate classes are homologous.     

Interleukin-6 and tumour necrosis factor alpha are expressed by keratinocytes but not by Langerhans cells.

The presence of human cytokines was examined in parallel skin biopsies and epidermal single cell preparations obtained from normal individuals. Using biotin-avidin-peroxidase and immunofluorescence techniques and antibodies against recombinant cytokines, a granular intercellular/membrane-associated staining for interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF alpha), but not IL-1 alpha or beta, was observed. An epidermal cytoplasmic staining pattern was also detected, which was most pronounced using the anti-rIL-6 antiserum. In the epidermal single cell preparations, membrane-associated staining was detected for both IL-6 and TNF alpha. Double staining revealed that CD1-positive Langerhans cells (LC) failed to express any of the examined cytokines. In vitro binding of rIL-6 or rTNF alpha to skin sections and epidermal single cell preparations indicated that the cell surface-associated IL-6 and TNF alpha originally demonstrated on keratinocytes were truly membrane-bound. Finally, co-cultivation of epidermal cells with an IL-6 responsive cell line, B9, and testing of epidermal cell supernatants in this assay, indicated that the in vivo membrane-bound IL-6 had biological activity.     

Elevated red cell adenosine deaminase activity: a marker of disordered erythropoiesis in Diamond-Blackfan anaemia and other haematologic diseases

Red-cell adenosine deaminase (ADA) activity in children with Diamond-Blackfan anaemia is significantly increased (1.91 +/- 0.90 U/g Hb) compared to that seen in transient erythroblastopenia of childhood (0.80 +/- 0.16 U/g Hb) or normal individuals (0.61 +/- 0.13 U/g). These data thus further support that measurement of this purine metabolic enzyme is useful in diagnosing the cause of pure RBC aplasia in children. Of interest, however, elevated RBC-ADA activity also is seen in some children with acute leukaemia and other haematologic disorders. In children with acute lymphoblastic leukaemia (ALL), the increase in RBC-ADA activity is proportional to the degree of anaemia. However, the elevated RBC-ADA activity in this leukaemic population is not related to the fetal haemoglobin concentration. These data suggest increased RBC-ADA activity may be a non-specific manifestation of abnormal erythroid stem cell function, an alteration distinct from that seen with reactivation of fetal erythropoiesis. However, since almost all patients with Diamond-Blackfan anaemia manifest elevated RBC-ADA activity, this chemical alteration yet may reflect the specific erythroid differentiation lesion in this disorder.     

Elastolytic activity of human monocytes from synovial fluid and blood of patients with arthritis. Relations to levels of interleukin 6 and soluble interleukin 2 receptor

Synovial fluid (SF) and blood from 24 patients with non-traumatic, sterile hydarthron were examined for monocyte elastolysis (M?E) and for levels of interleukin 6 (IL-6) and of soluble interleukin 2 receptor (sIL-2R). Six patients had osteoarthrosis (OA) and 18 patients had inflammatory hydarthron (IH), 10 of whom had rheumatoid arthritis (RA). Blood M?E was lower in OA than in IH, both measured as basal M?E activity and after in vitro stimulation with immune complexes and phorbol myristate acetate (PMA). SF M?E was higher than M?E in blood (p less than 0.01). This increase in SF M?E could be mimicked in vitro by prestimulation of blood M? with low levels of IC. SF IL-6 and sIL-2R were also elevated (p less than 0.01). All three parameters correlated to the degree of joint inflammation evaluated by SF leucocyte level, complement activation, blood C Reactive Protein, and to the clinical evaluation of the joint. The increase in SF M?E, IL-6 and sIL-2R in patients with IH, points to a stimulation of M? and lymphocytes in the joint.     

Sleep and its homeostatic regulation in mice lacking the adenosine A1 receptor

Sleep deprivation (SD) increases extracellular adenosine levels in the basal forebrain, and pharmacological manipulations that increase extracellular adenosine in the same area promote sleep. As pharmacological evidence indicates that the effect is mediated through adenosine A1 receptors (A1R), we expected A1R knockout (KO) mice to have reduced rebound sleep after SD. Male homozygous A1R KO mice, wild-type (WT) mice, and heterozygotes (HET) from a mixed 129/C57BL background were implanted during anesthesia with electrodes for electroencephalography (EEG) and electromyography (EMG). After 1 week of recovery, they were allowed to adapt to recording leads for 2 weeks. EEG and EMG were recorded continuously. All genotypes had a pronounced diurnal sleep/wake rhythm after 2 weeks of adaptation. We then analyzed 24 h of baseline recording, 6 h of SD starting at light onset, and 42 h of recovery recording. Neither rapid eye movement sleep (REM sleep) nor non-REM sleep (NREMS) amounts differed significantly between the groups. SD for 6 h induced a strong NREMS rebound in all three groups. NREMS time and accumulated EEG delta power were equal in WT, HET and KO. Systemic administration of the selective A1R antagonist 8-cyclopentyltheophylline (8-CPT) inhibited sleep for 30 min in WT, whereas saline and 8-CPT both inhibited sleep in KO. We conclude that constitutional lack of adenosine A1R does not prevent the homeostatic regulation of sleep.