Miltefosine (Impavido): the first oral treatment against leishmaniasis

Miltefosine is a novel antileishmanial drug that has significant selectivity in both in vitro and in vivo models. Clinical efficacy was demonstrated for the treatment of visceral leishmaniasis with the advantage of oral administration over the currently recommended antileishmanial drugs that require parenteral administration. Miltefosine produces high cure rates also in patients resistant to the standard antimonial therapy.     

Interepithelial cells of the oral mucosa in mice

Summary Non-epithelial mesenchymal and neuroectodermal cells occur between the keratinocytes in the stratified squamous epithelium of the oral mucosa. These cells cannot be classified adequately by light microscopy. In the present study the oral mucosa of the lip, cheek and tongue of 50 mice were studied by light and electron microscopy. 3,025 mononuclear interepithelial cells were documented and analysed.Monocytogenic macrophages, plasma cells and mast cells were not found interepithelially and cannot be regarded as a regular constituent of the epithelium. Only a few neuroectodermal cells — in mice these are exclusively Merkel cells, with no melanocytes — were localized in the epithelium. The majority of the interepithelial cell population is made up of lymphocytes (22.8%) and Langerhans cells (56.8%). They are an integral constituent of the epithelium. Lymphocytes with rounded and indented nuclei can be identified. The larger and dendritic Langerhans cells are a specific cell of squamous epithelium and also occur in the oral mucosa. Not all cells which feature the cytological characteristics of Langerhans cells contain Langerhans or Birbeck granules. Accordingly these granules cannot be considered an exclusive identification characteristic. Two types of Langerhans cells can be differentiated. 80.9% have the more or less typical appearance known from the epidermis and were termed macrophagocytoid Langerhans cells. The nuclei are irregularly indented and moderately heterochromatic. 19.1% possessed conspicuous large, spherical, euchromatic nuclei and an electron-lucent cytoplasm. These were termed reticuloid Langerhans cells. About 20% of the interepithelial cell population could not be identified, neither as typical lymphocytes nor as Langerhans cells. These were small to medium sized cells with deeply indented cerebriform strongly heterochromatic nuclei. They are similar to the Sézary cells or mycosis fungoides cells of epidermotropic human T-cell lymphomas. The lymphocytic nature of these cells has been confirmed. It seems likely that differentiation of lymphocytes to cerebriform cells occurs within the epithelium. It is further discussed whether cerebriform cells are precursors of Langerhans cells, a conclusion suggested morphologically by transitional forms. This would imply that Langerhans cells originate from lymphocytes, and that the cerebriform cell is an intermediate step of differentiation. The microenvironment of the squamous epithelium may play a role in the process of differentiation, which could explain the epitheliotropy of lymphocytes. The possibility is considered that Langerhans cells and interdigitating reticulum cells of the T-cell area of lymph nodes are identical. The close functional cooperation of Langerhans cells, lymphocytes, and interdigitating reticulum cells in immunological defenses against external antigens is discussed.The authors wish to express their sincere appreciation to Miss P. Starck and Miss I. Brandt for invaluable technical assistance in this project.     

鼻腔外侧壁的应用解剖

在60个头颅(男34,女26)120侧鼻腔外侧壁上观察测量了以下诸结构,结果:上鼻甲长15.9±2.9mm,宽4.7±1.1mm;中鼻甲长36.5±3.3mm,宽10.4±3.4mm;下鼻甲长42.7±3.6mm,宽12.3±1.7mm;半月裂长16.6±2.3mm;钩突长20.7±3.1mm,宽4.3±1.7mm;筛泡长19.2±4.1mm,高6.5±2.1mm,另外还测量了前鼻棘距上述各结构的距离.     

Proliferating cell nuclear antigen in malignant and pre-malignant lesions of epithelial origin in the oral cavity and the skin: an immunohistochemical study

Summary Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G₁ and S phase of the cell cycle and immunohistochemical detection of the protein represents a useful marker for the proliferating fraction of cells in tissue specimens. A series of malignant and pre-malignant lesions of the oral cavity and skin were evaluated by the streptavidin biotin immunoperoxidase method for detection of this protein. Monoclonal anti-PCNA antibody (PC 10) labelled proliferating cells in all cases with varying intensity of nuclear staining. In squamous cell carcinoma (n=48), PCNA positivity correlated with the differentiation and atypia of the tumour cells; however, in poorly differentiated tumours, the relationship between PCNA expression and proliferation was lost. Basal cell carcinoma showed an increased growth fraction in tiny epithelial nests (mean 43.8, SD 6.0,n=20) than in neoplastic basal cells (mean 30.1, SD 6.9,n=8). The growth fractions were significantly higher in the pre-malignant lesions (leukoplakia, mean 22.3, SD 7.7,n=14; Bowen's disease, mean 45.2, SD 11.7,n=12; senile keratosis, mean 41.2, SD 7.0,n=12) than in the normal mucosa (mean 9.8, SD 4.9,n=10), suggesting that cellular growth fractions correlate with the degree of dysplasia in pre-malignant lesions.     

Intermediate-term toxicity of repeated orally administered doses of the anti-malarial β-artemether in dogs

The artemisinin derivative beta-artemether, an anti-malarial, was evaluated for its toxicity and tolerability in a 2-week, multiple-dose study in dogs. Eight beagle dogs (4 females, 4 males) were given beta-artemether by oral gavage 3 times daily at 45 mg/kg/dosing (a total daily dose-level of 135 mg/kg) for 2 weeks. This beta-artemether dose regime was well tolerated. Body weight changes were normal although feed consumption during the treatment period reduced compared to that of the pre-trial period. Clinical signs were transient spells of soft to liquid feces. On completion of the treatment period, the animals were sacrificed and submitted to a full macroscopic post-mortem examination. Designated organs were weighed and a complete light microscopic examination was performed on 43 selected tissues from 1 animal per sex, and on the liver, kidneys, thymus, mandibular lymph nodes and lungs of the three other animals per sex. Major findings were high liver weight and histopathologic findings of slight diffuse hepatocellular hypertrophy and distal tubular dilatation, together with flattened epithelium, in the kidneys. With the dose regime used in this trial beta-artemether produced no clinical or apparent histopathological signs of neurotoxicity in dogs.     

The reproducibility of the oral glucose tolerance test over long (5 years) and short periods (1 week)

Summary Three oral glucose tolerance tests (oGTT) have been performed in 312 non-diabetic relatives of diabetics over a period of 10 years. In a second study 6 identical oGTT's have been performed at weekly intervals in 55 individuals. In this study the variance, calculated from the logarithmic values, increased in the following order: fasting (0.026), 1 h (0.035), 2 h (0.044) and 3 h values (0.047). The sum of the 1 h and 2 h values showed the lowest variance (0.024). No significant difference of the variances was found in the 43 individuals in whom both the long-term and the short-term studies have been performed. Thus, a great proportion of the total variance of glucose observed over longer periods only represents a random variation. This random variation is much higher than most other factors which might influence the result of an oGTT. A diagnosis based on a single oGTT is of only limited value.Supported by a grant from Deutsche Forschungsgemeinschaft (Ko 457/8)     

Representation of the body in the lateral striatum of the freely moving rat: single neurons related to licking

This study examined the relationship of single-neuron activity (n = 739), recorded from the lateral striatum of freely moving rats, to oral movements involved in licking single drops of liquid. Certain neurons (n = 74) fired specifically in relation to licking. Their firing rates increased during licking, but remained near zero in the absence of licking, throughout a full sensorimotor examination of the remainder of the orofacial area and all other body parts. Another category of neurons (n = 17) fired during licking but also fired in the absence of licking, during one or more other orofacial sensorimotor function(s). Lick-related neurons were located in the lateral striatum, throughout the entire anterior-posterior range studied (from +1.5 to -1.5 mm anterior-posterior, A-P, bregma = 0). Summed over the full A–P range, they were located significantly ventral to representations of the trunk and limbs. These findings extend the characterization of the somatotopic organization exhibited by lateral striatal neurons in the rat, to include representation of oral functions, consistent with converging evidence regarding the functional organization of the striatum.     

Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals

Antigen-driven tolerance is an effective method for suppression of autoimmune diseases. Adult animals can be tolerized against the induction of experimental autoimmune encephalomyelitis (EAE) by both oral and parenteral administration of myelin basic protein (MBP). We have found that in contrast to previous studies of neonatal tolerance in which parenterally administered autoantigens induced tolerance, the oral administration of MBP in neonatal rats did not result in tolerization to MBP, but instead, primed for immunologic responses. Proliferative responses to MBP and its encephalitogenic epitope were present in animals fed with MBP as neonates and co-culture of encephalitogenic T cells with cells from neonatal rats fed with MBP were associated with enhanced MBP responses rather than the suppression observed with cells from adult rats fed with MBP. Furthermore, neonates fed with MBP and immunized 6–8 weeks later with MBP in adjuvant to induce EAE revealed enhancement of disease severity, and were not protected from a second attack upon active reinduction of EAE. Subcutaneous injection of soluble MBP into neonates had no effect on EAE induction as adults, whereas intraperitoneal injection of MBP in neonates was associated with marked suppression of disease in adults. Suppression of EAE began to appear in animals fed with MBP at 4 weeks of age, and was similar to oral tolerance in adult animals when animals were fed at 6 weeks of age. These results suggest that immaturity of the immunoregulatory network associated with oral tolerance and sensitization to autoantigens via the gut in the neonatal period may contribute to the pathogenesis of autoimmune diseases.     

Availability of glucose ingested during muscle exercise performed under acipimox-induced lipolysis blockade

This study investigated the percentage of carbohydrate utilization than can be accounted for by glucose ingested during exercise performed after the ingestion of the potent lipolysis inhibitor Acipimox. Six healthy male volunteers exercised for 3 h on a treadmill at about 45% of their maximal oxygen uptake, 75 min after having ingested 250 mg of Acipimox. After 15-min adaptation to exercise, they ingested either glucose dissolved in water, 50 g at time 0 min and 25 g at time 60 and 120 min (glucose, G) or sweetened water (control, C). Naturally labelled [¹³C]glucose was used to follow the conversion of the ingested glucose to expired-air CO₂. Acipimox inhibited lipolysis in a similar manner in both experimental conditions. This was reflected by an almost complete suppression of the exercise-induced increase in plasma free fatty acid and glycerol and by an almost constant rate of lipid oxidation. Total carbohydrate oxidation evaluated by indirect calorimetry, was similar in both experimental conditions [C, 182, (SEM 21); G, 194 (SEM 16) g · 3 h^–1], as was lipid oxidation [C, 57 (SEM 6); G, 61 (SEM 3) g · 3 h^–1]. Exogenous glucose oxidation during exercise G, calculated by the changes in¹³C:¹²C ratio of expired air CO₂, averaged 66 (SEM 5) g · 3 h^–1 (19% of the total energy requirement). Consequently, endogenous carbohydrate utilization was significantly smaller after glucose than after placebo ingestion: 128 (SEM 18) versus 182 (SEM 21) g · 3 h^–1, respectively (P < 0.05). Symptoms of intense fatigue and leg cramps observed with intake of sweet placebo were absent with glucose ingestion.In conclusion, we found glucose ingestion during 3-h exercise with lipolysis blockade could provide metabolic substrate permitting a significant sparing of endogenous carbohydrate and consequently an improvement in performance.     

Radiologic anatomy of the metacarpophalangeal joints II to V

Summary The metacarpophalangeal (MCP) joints II to V of 21 hands were examined radiologically and arthrographically. Different recesses of the joint cavity were demonstrated both radiologically and macroscopically, with a dominating dorsal recess. The existing forms of the dorsal recess were one-tailed, two-tailed, three-tailed, symmetric and caplike. Additionally, a palmar recess was found in the specimens examined, which presented as a small protrusion of the capsule and lay between the metacarpal head and the palmar plate. Furthermore, a distal recess was filled and unfolded in almost all the cases. Lateral recesses were found in the radial and ulnar directions beneath the collateral ligaments. The dorsal recess, due to its ability to collect fluid, is of clinical importance in pathologic processes causing effusions, while the clinical importance of the lateral recesses lie in their proximity to the stabilizing collateral ligaments of the metacarpophalangeal joints. The above mentioned recesses were seen as normal formations of the MCP joints and should therefore be taken into account in pathologic processes in this area.

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Radioanatomie des articulations métacarpo-phalangiennes des 2ème au 5ème doigts

Résumé Les articulations métacarpophalangiennes (MCP) des 2ème au 5ème doigts de 21 mains ont été explorées en radiographie standard et en arthrographie. Plusieurs récessus articulaires, dont un récessus dorsal prédominant, ont été mis en évidence à la fois sur les radiographies et macroscopiquement. Les récessus dorsaux observés pouvaient comprendre une, deux ou trois cornes ou prendre un aspect de coiffe. Un récessus palmaire a été également trouvé sur 49 pièces sous la forme d'une petite expansion capsulaire entre la tête métacarpienne et la plaque palmaire. Un récessus distal était de plus rempli dans presque tous les cas. Des récessus latéraux étaient trouvés sur les bords radial et ulnaire, entre les ligaments latéraux. Les épanchements articulaires se collectent volontiers dans le récessus dorsal qui se manifeste cliniquement. Les récessus latéraux sont cliniquement intéressants par leur proximité avec les ligaments latéraux des MCP. Les récessus décrits sont des structures normales des MCP et ne doivent pas être pris pour des éléments pathologiques.