The attachment and entry of Leishmania (Leishmania) major into macrophages: observation by scanning electron microscope

Leishmaniasis, a zoonotic protozoan disease, starts with the inoculation of the Leishmania promastigotes into the skin at the time of blood ingestion by a female sandfly. The infection of leishmaniasis is established when the Leishmania organisms start their own intracellular multiplication after having been phagocytized by the host's macrophages. In the earliest stage of the infection, therefore, the attachment of the promastigates to the macrophages is essential. We incubated a mixed culture of macrophages (JM774-1A) and Leishmania (Leishmania) major for 6 hours in vitro and observed the process of the attachment between the parasite and host cell by scanning electron microscope. We found for the first time that the attachment between the two occurred at the site of the parasite body, in addition to the previously reported sites of the flagellar tip, flagellar base, and aflagellar tip (posterior pole).     

Cardiovascular changes in preeclampsia

The cardiovascular system undergoes a host of changes in association with the development of preeclampsia, which ultimately lead to the classic low cardiac output-high systemic vascular resistant state. A newer hypothesis suggests that exaggeration of the normal for pregnancy hyperdynamic, low-resistance state commencing in early gestation is responsible for the genesis of the clinically apparent vasoconstrictive disease in late pregnancy. Such events may also lead to the vascular damage that persists into later life. In preeclampsia, cardiac contractility is preserved but both steady and pulsatile arterial load are increased inappropriately, failing to decrease as would occur in normal pregnancy, involving both conduit and small vessels. Abnormal adaptive mechanisms may be secondary to changes in vascular tone or vascular wall elements, and may have future implications for a woman later in life.     

Somatostatin and gamma-aminobutyric acid inhibit interleukin-1 beta-stimulated release of interleukin-6 from rat C6 glioma cells

OBJECTIVE: We investigated the ability of inhibitory neurotransmitters to alter the interleukin-1 beta (IL-1 beta)-stimulated release of interleukin-6 (IL-6) from cultured glial tumor cells. METHODS: C6 rat glioblastoma cells were exposed to either IL-1 beta or its putative second messenger lysophosphatidylcholine (LPC) in the absence or presence of the inhibitory neurotransmitters somatostatin (SRIF) or gamma-aminobutyric acid (GABA). Alternatively, C6 cells were pretreated with selective inhibitors of JNK or p38 and then exposed to either IL-1 beta or LPC to determine the relative involvement of these terminal stress kinases in the stimulation of IL-6 release. RESULTS: IL-1 beta promoted the release of IL-6 with a maximally effective concentration of 25 ng/ml. Both SRIF-14 and SRIF-28 comparably suppressed stimulated IL-6 release with an ED(50) of approximately 50 nM. GABA also prevented IL-1 beta-driven IL-6 release (ED(50) = 100 microM). IL-1 beta and LPC synergistically enhanced release of IL-6 in the presence of the beta-adrenergic receptor agonist isoproterenol (ISO); these effects were largely reversed by SRIF or GABA. The pyridinylimidazole inhibitor of p38, SB-203580, completely blocked stimulation of IL-6 release by IL-1 beta or LPC; conversely, the anthrapyrazolone JNK inhibitor, SP-600125, was ineffective in modifying stimulated IL-6 release. CONCLUSIONS: The effects of IL-1 beta and LPC on IL-6 release from glioma cells are effectively antagonized by the inhibitory neurotransmitters SRIF and GABA. On the basis of correlative studies, we propose that the ability of inhibitory transmitters such as SRIF and GABA to counter the induction of IL-6 release may entail suppression of p38 activity.     

Graspable objects grab attention when the potential for action is recognized

Visually guided grasping movements require a rapid transformation of visual representations into object-specific motor programs. Here we report that graspable objects may facilitate these visuomotor transformations by automatically grabbing visual spatial attention. Human subjects viewed two task-irrelevant objects--one was a 'tool', the other a 'non-tool'--while waiting for a target to be presented in one of the two object locations. Using event-related potentials (ERPs), we found that spatial attention was systematically drawn to tools in the right and lower visual fields, the hemifields that are dominant for visuomotor processing. Using event-related fMRI, we confirmed that tools grabbed spatial attention only when they also activated dorsal regions of premotor and prefrontal cortices, regions associated with visually guided actions and their planning. Although it is widely accepted that visual sensory gain aids perception, our results suggest that it may also have consequences for object-directed actions.     

Sinovenous thrombosis in children

Sinus thrombosis in children is increasingly recognized; however, the diagnosis is still frequently missed. Children may have an increased incidence of this disorder compared with adults, and neonates are at greatly increased risk compared with older children. Childhood CSVT carries significant long-term sequelae that include death or neurologic deficits in nearly 50% of cases. Neonates are not spared from these sequelae. At present, the approach to treatment is empiric but in the past decade treatment with anti-coagulants is supported by the unacceptable rates of adverse outcomes, the pathophysiology of CSVT, and the data supporting the efficacy and safety of anti-coagulation for adult CSVT. Among the most significant current and future developments in childhood CSVT is the evolution of accurate, noninvasive and economical neuroimaging techniques. The latter techniques have the potential to increase the detection rate of childhood CSVT, improve our understanding of the pathophysiology and define important subgroups of patients who best respond to treatment. An international interest in childhood CSVT is developing and, in the next decade, will enable the necessary multi-national clinical trials to provide evidence-based treatments and decrease the adverse outcomes.     

Distension technique to improve computed tomographic evaluation of oral cavity lesions

BACKGROUND: The apposing mucosa of the oral cavity makes the computed tomographic identification of a clinically obvious mass difficult. Contrast distension techniques have been used in radiology to evaluate for presence of a "hidden" mass. OBJECTIVE: To illustrate the utility of distending the oral cavity with air, water, or contrast to display otherwise obscure oral cavity lesions. PATIENTS AND METHODS: In 3 normal subjects and 5 patients with biopsy-proved oral cavity lesions, serial contiguous 3-mm axial and coronal computed tomographic scans were obtained before and after distension of the oral cavity using intraoral air or water. Air distension was achieved by having the subjects perform a modified Valsalva maneuver during the scan acquisitions. Fluid distension was obtained using approximately 40 mL of water. RESULTS: In each case, the contrast successfully distended the oral cavity, separating the mucosal surfaces. Gingivobuccal lesions that were obscured by apposition of the lips and cheeks to the gums and teeth, or by apposition of the tongue to the inner margins of the gums and teeth, were clearly demonstrated. Lesions involving or extending into the retromolar trigone were also well demonstrated using this distension technique. CONCLUSIONS: Computed tomographic display of the anatomy and pathology of the oral cavity can be improved simply by distending the oral cavity using air or water as a contrast medium. This technique successfully shows lesions that are obscured by the apposing surfaces of the vestibule and the oral cavity proper, improving computed tomographic diagnosis.     

Bone and joint complications related to Gaucher disease

There is a broad spectrum of Gaucher disease-related skeletal complications, ranging from asymptomatic osteopenia to osteonecrosis (of the shoulders and hips) with secondary degenerative joint disease. Characterization of the pattern and severity of bone involvement in the individual patient requires the application of conventional and advanced radiographic techniques. The introduction of enzyme replacement therapy (ERT) for this inborn error of glycosphingolipid metabolism has focused great interest in determining the nature and extent of the bone responses with this mode of treatment. The multifactorial etiology of the bone complications necessitates a multifaceted approach, combining pharmacologic strategies with physical therapy and orthopedic intervention. As bone disease can lead to chronic pain and debility with a resultant adverse impact on quality of life, it is important that patients be monitored closely and that early intervention with ERT prior to established bone disease (infarction and fibrosis) be considered.     

Gamma-knife radiosurgery for trigeminal neuralgia

Gamma knife was installed at the PD Hinduja National Hospital and Medical Research Centre, Mumbai, India, in January 1997. In the first year of gamma-knife radiosurgery to January 1998, we treated 110 patients, of whom six had medically refractory trigeminal neuralgia. Seven treatments were administered to this group of six patients (one had bilateral neuralgia). This report evaluates the effectiveness of radiosurgery treatment in these patients. The median age of the patients was 56 years and there were five males and one female. Following Leksell stereotactic frame fixation, a magnetic resonance imaging scan was done in all. The Leksell gamma plan was used for planning. A radiosurgery dose of 70–80 Gy was delivered to the trigeminal root entry zone, 2–4 mm anterior to the junction of the pons and trigeminal nerve with a single 4 mm collimator helmet. Complete pain relief was achieved in four patients. Two had partial relief. No patient developed any radiosurgery related morbidity during the follow-up period of 5–16 months. Radiosurgery seems to be an effective approach for medically or surgically refractory trigeminal neuralgia.     

Cardiovascular system during the postpartum state in women with a history of preeclampsia

In subjects with previous preeclampsia, differences in cardiovascular and/or blood biochemical parameters are present in the nonpregnant state, and a simultaneous assessment of multiple derived indices better differentiates between women with or without previous preeclampsia. We examined 18 previous preeclamptic and 50 previous uncomplicated pregnancies, ≈16 months postpartum. Cardiovascular assessment included the following: (1) systemic hemodynamics and mechanics (Doppler echocardiography, tonometry, and oscillometric sphygmomanometry); (2) endothelial function (plethysmography); (3) left ventricular properties (echocardiography); and (4) blood biochemical analyses. Compared to women with previous uncomplicated pregnancies, previous preeclamptics had higher mean (80±1 versus 86±3 mm Hg; P=0.04) and diastolic (64±1 versus 68±2 mm Hg; P=0.04) pressures and total vascular resistance (1562±37 versus 1784±114 dyne · s/cm(5); P=0.03). Systolic blood pressure, arterial compliance, and left ventricular properties were not different. Although heart-to-femoral pulse wave velocity was not different, heart-to-brachial pulse wave velocity tended to be faster in previous preeclamptics (374±8 versus 404±20 cm/s; P=0.06). Stress-induced increase in forearm blood flow was less in previous preeclamptics (245%±21% versus 136%±22%; P=0.01), indicating impaired endothelial function. No significant differences were observed in markers of endothelial activation, dyslipidemia, or oxidative stress; previous preeclamptics tended to have higher glucose level (58.7±1.9 versus 95±5.2 mg/dL; P=0.06). Logistic regression analysis indicated that a simultaneous evaluation of multiple derived indices better discriminated between the 2 groups. The differences in the previous preeclamptic group are in directions known to be associated with greater cardiovascular disease risk later in life.