EFFECT OF DIETARY FISH OILS ON THE FORMATION OF LEUKOTRIENE B4 AND B5, THROMBOXANE AND PLATELET ACTIVATING FACTOR BY RAT LEUKOCYTES

1. This study investigates the effect of dietary eicosapentaenoic acid (EPA), in the form of 'Max EPA' fish oil, on leukotriene B4 (LTB4) production in ionophore-stimulated rat leukocytes. Male Wistar rats (200-250 g) were fed for 3 weeks on a synthetic chow supplemented with either 10% by weight Max EPA oil or a coconut oil/safflower oil mixture. 2. The EPA-rich diet significantly increased the EPA content of leukocyte phospholipids and decreased the arachidonic acid level by 35% (P less than 0.001) compared with the control diet. 3. The concentration of leukotrienes in the ionophore (A23187) stimulated leukocytes was measured by reverse-phase HPLC using prostaglandin B2 as the internal standard. The EPA-supplemented diet caused a 50% decrease in LTB4 production (P less than 0.001) and a concomitant increase in the formation of the biologically less active LTB5 compared with the control diet. The amount of LTB4 and LTB5 produced by stimulated leukocytes closely resembled the changes in arachidonic acid and EPA content of leukocyte phospholipids. 4. Thromboxane B2 (TxB2) production in stimulated leukocytes from the EPA-fed animals was also decreased compared with the control group. 5. Although the formation of platelet activating factor by stimulated leukocytes was not altered by dietary treatment, the ability of an EPA-rich diet to decrease LTB4 and TxB2 production suggests that these diets may attenuate leukocyte activity and have useful anti-inflammatory effects.     

A Numerical Analysis of the Geniculocortical Input to Striate Cortex in the Monkey

Using data that are available in various publications, a quantitativeanalysis has been made of the geniculocortical input to layerIVC of the macaque striate cortex. The data suggest that only1.3–1.9% of the excitatory, or asymmetric synapses inlayer IVC     

Cerebrospinal fluid involvement in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an aggressive neoplasm that is incurable by standard therapy. Patients often present with high-stage disease (Stages III-IV) and frequently have involvement at multiple extranodal sites. Although the gastrointestinal tract, spleen, lung, pleura, bone marrow, and peripheral blood are among the most commonly involved tissues, MCL may also disseminate to so-called sanctuary sites including the central nervous system. Despite this, current clinical evaluations do not routinely include assessment of the cerebrospinal fluid (CSF) for lymphomatous infiltrates at presentation, and moreover, only few authors have specifically examined CSF involvement in MCL. In this study, we reviewed the medical records of 108 patients with MCL seen at three centers over a 5-year period to determine the rate of CSF sampling and the frequency of CSF involvement by MCL. The clinical and cytologic characteristics associated with CSF involvement were also studied. Central nervous system (CNS) signs and/or symptoms prompted CSF sampling in 25/108 patients (23%). Specific radiographic abnormalities were present in 9/25 patients (36%). CSF involvement by MCL was identified in 10 of the 25 CSF-sampled patients (40%) by morphology (3 patients), flow cytometry alone (1 patients), or both (6 patients). The CSF-positive cases included two blastoid variants. The CSF cytology of the nine morphologically positive cases was pleomorphic, and prominent cytoplasmic granules were observed in two cases. The overall rate of CSF involvement by MCL among the cohort was 9%, which is comparable to that reported in other selected studies examining this issue.     

Parasite uptake of desferroxamine: a prerequisite for antimalarial activity

Desferroxamine has been shown to exhibit potent antimalarial activity. However, it is unclear as to whether desferroxamine functions by the chelation of extracellular, intra-erythrocytic, or parasite-associated iron. In order to determine desferroxamine's site of action, we have employed a large molecular weight dextran derivative of desferroxamine (70 kDa) and a reversible osmotic lysis technique by which erythrocytes were intracellularly loaded with this chelator. The desferroxamine-dextran derivative has virtually identical iron-binding characteristics to desferroxamine but, unlike desferroxamine, it is unable to cross the erythrocyte membrane. As previously shown, desferroxamine added to culture media exhibited potent antimalarial activity (mean effective inhibitory dose (ED50) approximately 6 microM). However, extracellular desferroxamine-dextran showed antimalarial activity only at very high doses (ED50 greater than or equal to 180 microM), indicating that extracellular iron chelation is not involved in the antimalarial activity of desferroxamine. The intra-erythrocytic entrapment of the desferroxamine-dextran derivative also had no significant effect, except at very high concentrations, demonstrating that desferroxamine does not remove a non-haem iron source necessary for malarial replication. The results of this study clearly suggests that the antimalarial activity of desferroxamine is directly related to its ability to enter the parasitic compartment and not due to the chelation of extra- or intra-erythrocytic iron pools necessary for malarial growth.     

The role of glucocorticoids and prostaglandin E2 in the recruitment of bone marrow mesenchymal cells to the osteoblastic lineage: Positive and negative effects

The role of glucocorticoids in bone formation presents a problem because although pharmacological doses in vivo give rise to osteoporosis, physiological concentrations are required for osteoblast (OB) differentiation in vitro. To try and rationalize this dichotomy, we investigated the effect of dexamethasone on the recruitment of OB precursors present in bone marrow. Using the CFU-f assay, we can measure (1) total colony formation; (2) the osteoblastic differentiation of the colonies defined as their ability to express alkaline phosphatase, synthesize collagen, and to calcify; and (3) colony expansion as either average colony surface area or average colony number. In control cultures and in the presence of 10⁻¹⁰–10⁻⁹ M dexamethasone, colony formation and total cell number was maximal, but the addition of PGE₂ had no effect on colony number and very few colonies expressed the OB phenotype. In the presence of 10⁻⁸–10⁻⁷ M dexamethasone, colony numbers and total cell numbers were reduced but were increased by the addition of PGE₂, the average colony cell number and surface area were relatively unchanged and a proportion of the colonies expressed APase, calcified and synthesized collagen. In cultures containing 10⁻⁶–10⁻⁵ M dexamethasone, colony numbers were further reduced but were stimulated by the addition of PGE₂ and some colonies differentiated; however, colony expansion was dramatically reduced by up to 80%. These results suggest that physiological levels of glucocorticoids are necessary for OB differentiation and allow the control of OB recruitment by PGE₂. High levels of glucocorticoids drastically reduce proliferation of the OB precursors leading to glucocorticoid-induced osteoporosis. Received: 8 May 1995 / Accepted: 23 February 1996     

Implantation of penile prostheses in patients impotent after priapism

Review of recent implantations of penile prostheses done at Duke University Medical Center reveals 6 patients implanted for impotence secondary to priapism. Of these 6 patients, 5 had sickle cell anemia-induced priapism and 1 had idiopathic priapism. One patient had implantation of an inflatable prosthesis later followed by a semirigid prosthesis, 3 had implantation of a semirigid prosthesis, and 1 had an unsuccessful attempt at implantation of a semirigid prosthesis. The 5 patients with successful implantation have obtained satisfactory postoperative coital function. We believe that penile prostheses are beneficial in patients with impotence secondary to priapism. The degree of fibrosis encountered suggests that a semirigid prosthesis is more favorable, since the inflatable prosthesis may not overcome corporeal rigidity.     

The microvasculature and microcirculation of the peri-macular capillary network. New diagnostic possibilities with the scanning laser ophthalmoscope]

The scanning laser technique makes it possible for the first time to perform objective measurements of blood flow velocities in retinal capillaries. This new technique allows for continuous recording of retinal pictures at high resolution. Only the quality of the optical media of the eye limits the resolution of the retinal image. Sequences with a sample frequency of up to 50 images/s can be stored using a digital recorder. In these digital sequences the moving blood stream in retinal capillaries is visible. Segments of high and low fluorescence can be observed moving through the capillary network of the perifoveal capillaries. The flow velocities of these segments can be measured objectively using image analysis. In addition, morphologic information about the perifoveal capillary bed can be obtained by this new technique. Determination of flow velocities and morphological parameters give an objective means of assessing oxygen supply to the macular tissue. Furthermore, the degree of changes in the perifoveal microcirculation may provide objective data for estimating the prognosis of diabetic or senile maculopathy. Further investigation is needed to examine the relationship between changes in perifoveal microcirculation and the development of macular edema in various diseases.     

p53 Hot-Spot Mutational Analysis in Advanced Western Gallbladder Carcinoma

p53 tumor suppressor gene, have been focusing on this gene’s immunohistochemical detection. From November 1991 to October 1993, seven patients suffering from gallbladder carcinoma underwent surgical resection. Cancerous and normal liver tissues were obtained immediately after surgery, snap-frozen in liquid nitrogen, and stored at −80°C for immunohistochemistry and DNA isolation. Exons 5, 6, 7, and 8 of the p53 gene were completely sequenced following polymerase chain reaction (PCR) amplification of a 1574-bp fragment. Missense mutations were detected in the cancerous tissues of two patients: one transition each on codons 134 (Phe→Leu) and 146 (Trp→Arg). Immunohistochemical p53 staining was positive in the latter patient only. This is the first report on sequence analysis and mutagenesis of the p53 gene in Caucasian patients with gallbladder cancer. Both mutations were transitions and seem to represent a rather rare event. The possible impact of p53 mutagenesis on gallbladder tumorigenesis requires evaluation in larger studies.     

Gamekeeper thumb: Diagnosis of ulnar collateral ligament injury using magnetic resonance imaging,magnetic resonance arthrography and stress radiography

Ulnar collateral ligament (UCL) tears may be nondisplaced or displaced relative to the adductor pollicis aponeurosis. Nondisplaced tears typically heal with immobilization whereas displaced tears require surgery. Nineteen patients with UCL injuries were evaluated using MR imaging (MRI), MR arthrography, and stress radiography (SR) to determine the efficacy of these techniques in differentiating nondisplaced from displaced UCL tears. Nineteen patients with UCL injuries were evaluated. MRI was utilized in 5 patients, and MR arthrography in 14, with 12 of these 14 undergoing SR. They were followed until resolution of symptoms; those without relief, and those with suspected displaced UCL tears were surgically explored. Surgery and imaging was correlated. Eight patients underwent surgical repair. SR was abnormal in six patients treated surgically, but was negative in four of six conservatively treated patients with MR findings of nondisplaced tears. All patients with MR or MR arthrographic findings interpreted as being normal or as having a nondisplaced tear improved after conservative treatment. Based on surgical findings and clinical follow-up, MR arthrography accurately diagnosed 13 of 14 UCL injuries, with one false-positive interpretation. SR is often falsely negative. MR imaging with or without intra-articular contrast injection proved to be accurate in a small series of patients with UCL injuries.