Heterozygote carriers of mutations in the F11 gene, encoding Factor XI, have normal coagulation by thromboelastography during pregnancy.

BACKGROUND: Evidence to guide clinical decision-making in pregnant women who are usually asymptomatic, but identified as heterozygote carriers of F11 mutations, is lacking. We hypothesized that women identified on prenatal screening as heterozygous for a mutation in the F11 allele would have minimal evidence of an in vitro coagulation abnormality. METHODS: We prospectively enrolled women identified by prenatal screening as F11 mutation carriers and pregnant women who were presumed to be normal as controls. We collected blood during antepartum visits or at presentation for delivery and assessed Factor XI (FXI) coagulant activity level, as well as whole-blood coagulation, by thromboelastography. RESULTS: F11 mutation carriers had lower serum FXI activity levels than controls (51.2 ±â€¯8.5% vs 94.1 ±â€¯19.4%; P <0.0001). Thromboelastography values of all control subjects and F11 mutation carriers were within the normal range. The R-time was slightly longer in F11 mutation carriers (5.3 ±â€¯1.0 s vs 4.2 ±â€¯0.8 s, P <0.002), but no other statistically significant differences in thromboelastogram parameters were identified between groups. CONCLUSIONS: Despite lower FXI activity in the F11 mutation group, we found minimal differences in whole-blood measures of coagulation using thromboelastography. These findings support our hypothesis that a single copy of an F11 mutation does not produce significant evidence of an in vitro coagulation abnormality. Thromboelastography might be useful in determining the risk of neuraxial anesthesia in pregnant women, but additional work is required to establish the validity of this test.

Associations of coffee consumption with markers of liver injury in the insulin resistance atherosclerosis study.

BACKGROUND: Coffee consumption has been associated with reduced risk of developing type 2 diabetes mellitus (T2DM) however, the mechanism for this association has yet to be elucidated. Non-alcoholic fatty liver disease (NAFLD) characterizes and predicts T2DM yet the relationship of coffee with this disorder remains unclear. Our aim was to investigate the associations of coffee with markers of liver injury in 1005 multi-ethnic, non-diabetic adults in the Insulin Resistance Atherosclerosis Study. METHODS: Dietary intake was assessed using a validated 114-item food frequency questionnaire. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and fetuin-A were determined in fasting blood samples and the validated NAFLD liver fat score was calculated. Multivariate linear regression assessed the contribution of coffee to variation in markers of liver injury. RESULTS: Caffeinated coffee showed significant inverse associations with ALT (ß = -0.08, p = 0.0111), AST (ß = -0.05, p = 0.0155) and NAFLD liver fat score (ß = -0.05, p = 0.0293) but not with fetuin-A (ß = 0.04, p = 0.17). When the highest alcohol consumers were excluded, these associations remained (ALT ß = -0.11, p = 0.0037; AST ß = -0.05, p = 0.0330; NAFLD liver fat score ß = -0.06, p = 0.0298). With additional adjustment for insulin sensitivity, the relationship with ALT remained significant (ALT ß = -0.08, p = 0.0400; AST ß = -0.03, p = 0.20; NAFLD liver fat score ß = -0.03, p = 0.27). There were no significant associations of decaffeinated coffee with liver markers. CONCLUSIONS: These analyses indicate a beneficial impact of caffeinated coffee on liver morphology and/or function, and suggest that this relationship may mediate the well-established inverse association of coffee with risk of T2DM.

Comparison of a rebound tonometer with an applanation tonometer in dogs with glaucoma.

Eighteen dogs which presented to the Purdue University Ophthalmology Service with a final diagnosis of primary or secondary glaucoma, and 5 dogs with normal eye examinations, were evaluated. Each dog underwent a complete ophthalmic examination. An eye was categorised as glaucomatous if an intraocular pressure (IOP) measurement ≥25 mm Hg was obtained, and clinical signs consistent with glaucoma were present. Readings with the TonoVet were always performed first without topical anaesthesia. After obtaining readings with the TonoVet, one drop of proparacaine was applied to each eye, followed by IOP measurement with the Tono-Pen XL. As IOP increased, the difference between measurements obtained with the two tonometers was statistically significant. The TonoVet consistently gave higher IOP values compared with the Tono-Pen XL in glaucomatous eyes with Tono-Pen XL IOP readings ≥25 mm Hg. IOP readings were not significantly different between tonometers for normotensive eyes. Based on the results of the current study, the same device should be used for monitoring of IOP in individual patients.

Post-anesthetic cortical blindness in cats: twenty cases.

The medical records of 20 cats with post-anesthetic cortical blindness were reviewed. Information collected included signalment and health status, reason for anesthesia, anesthetic protocols and adverse events, post-anesthetic visual and neurological abnormalities, clinical outcome, and risk factors. The vascular anatomy of the cat brain was reviewed by cadaver dissections. Thirteen cats were anaesthetised for dentistry, four for endoscopy, two for neutering procedures and one for urethral obstruction. A mouth gag was used in 16/20 cats. Three cats had had cardiac arrest, whereas in the remaining 17 cases, no specific cause of blindness was identified. Seventeen cats (85%) had neurological deficits in addition to blindness. Fourteen of 20 cats (70%) had documented recovery of vision, whereas four (20%) remained blind. Two cats (10%) were lost to follow up while still blind. Ten of 17 cats (59%) with neurological deficits had full recovery from neurological disease, two (12%) had mild persistent deficits and one (6%) was euthanased as it failed to recover. Four cats (23%) without documented resolution of neurological signs were lost to follow up. Mouth gags were identified as a potential risk factor for cerebral ischemia and blindness in cats.

Association of high viral load and abnormal liver function with high aflatoxin B1-albumin adduct levels in HIV-positive Ghanaians: preliminary observations.

We examined the association between certain clinical factors and aflatoxin B(1)-albumin adduct (AF-ALB) levels in HIV-positive people. Plasma samples collected from 314 (155 HIV-positive and 159 HIV-negative) people were tested for AF-ALB levels, viral load, CD4+ T-cell count, liver function profile, malaria parasitaemia, and hepatitis B and C virus infections. HIV-positive participants were divided into high and low groups based on their median AF-ALB of 0.93 pmol mg(-1) albumin and multivariable logistic and linear regression methods used to assess relationships between clinical conditions and AF-ALB levels. Multivariable logistic regression showed statistically significant increased odds of having higher HIV viral loads (OR=2.84; 95% CI=1.17-7.78) and higher direct bilirubin levels (OR=5.47; 95% CI=1.03-22.85) among HIV-positive participants in the high AF-ALB group. There were also higher levels of total bilirubin and lower levels of albumin in association with high AF-ALB. Thus, aflatoxin exposure may contribute to high viral loads and abnormal liver function in HIV-positive people and so promote disease progression.

(R)-roscovitine prolongs the mean open time of unitary N-type calcium channel currents.

(R)-roscovitine (Ros) is a cyclin-dependent kinase inhibitor that also has been shown to have direct agonist and antagonist actions on Ca(v)2.1 (P/Q-type) and Ca(v) 2.2 (N-type) families of voltage-gated calcium channels. These kinase-independent effects represent a novel opportunity to advance our understanding of calcium channel function and calcium-triggered neurotransmitter release. Furthermore, such actions on calcium channels may direct the development of Ros derivatives as new therapeutic agents. We used patch clamp recordings to characterize mechanisms that underlie the agonist effects of Ros on unitary N-type calcium channel gating. We found that N-type channels normally gate with either a short or long mean open time, that Ros significantly prolonged the mean open time of the long gating component and increased the probability of observing channels that gated with a long open time, but had no effect on single channel conductance. Using Monte Carlo simulations of a single channel kinetic model and Ros interactions, we were able to reproduce our experimental results and investigate the model's microscopic dynamics. In particular, our simulations predicted that the longer open times generated by Ros were due to the appearance of a long open state combined with an increased amount of time spent in transitions between open states. Our results suggest a mechanism for agonist effects of Ros at the level of single channels, and provide a mechanistic explanation for previously reported agonist effects on whole cell calcium currents.

Expression of GABA(A) receptor alpha3-, theta-, and epsilon-subunit mRNAs during rat CNS development and immunolocalization of the epsilon subunit in developing postnatal spinal cord.

Ionotropic GABA(A) receptors are heteromeric structures composed of a combination of five from at least 16 different subunits. Subunit genes are expressed in distinct cell types at specific times during development. The most abundant native GABA(A) receptors consist of alpha1-, beta2-, and gamma2-subunits that are co-expressed in numerous brain areas. alpha3-, theta-, And epsilon-subunits are clustered on the X chromosome and show striking overlapping expression patterns throughout the adult rat brain. To establish whether these subunits are temporally and spatially co-expressed, we used in situ hybridization to analyze their expression throughout rat development from embryonic stage E14 to postnatal stage P12. Each transcript exhibited a unique or a shared regional and temporal developmental expression profile. The thalamic expression pattern evolved from a restricted expression of epsilon and theta transcripts before birth, to a theta and alpha3 expression at birth, and finally to a grouped epsilon, theta and alpha3 expression postpartum. However, strong similarities occurred, such as a grouped expression of the three subunits within the hypothalamus, tegmentum and pontine nuclei throughout the developmental process. At early stages of development (E17), epsilon and theta appeared to have a greater spatial distribution before the dominance of the alpha3 subunit transcript around birth. We also revealed expression of alpha3, theta, and epsilon in the developing spinal cord and identified neurons that express epsilon in the postnatal dorsal horn, intermediolateral column and motoneurons. Our findings suggest that various combinations of alpha3-, theta- and epsilon-subunits may be assembled at a regional and developmental level in the brain.

Sickle Cell Disease in the Post Genomic Era: A Monogenic Disease with a Polygenic Phenotype.

More than half a century after the discovery of the molecular basis of Sickle Cell Disease (SCD), the causes of the phenotypic heterogeneity of the disease remain unclear. This heterogeneity manifests with different clinical outcomes such as stroke, vaso-occlusive episodes, acute chest syndrome, avascular necrosis, leg ulcers, priapism and retinopathy. These outcomes cannot be explained by the single mutation in the beta-globin gene alone but may be attributed to genetic modifiers and environmental effects. Recent advances in the post human genome sequence era have opened the door for the identification of novel genetic modifiers in SCD. Studies are showing that phenotypes of SCD seem to be modulated by polymorphisms in genes that are involved in inflammation, cell-cell interaction and modulators of oxidant injury and nitric oxide biology. The discovery of genes implicated in different phenotypes will help understanding of the physiopathology of the disease and aid in establishing targeted cures. However, caution is needed in asserting that genetic modifiers are the cause of all SCD phenotypes, because there are other factors such as genetic background of the population, environmental components, socio-economics and psychology that can play significant roles in the clinical heterogeneity.

High-level cerebellar expression of cytokines and adhesion molecules in fatal, paediatric, cerebral malaria.

Although the roles played by systemic tumour necrosis factor (TNF) and interleukin 1beta (IL-1beta), and their upregulation of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin, in the pathogenesis of human cerebral malaria (CM) are well established, the role of local cytokine release, in the brain, remains unclear. Immunohistochemistry was therefore used to compare the expression of ICAM-1, VCAM-1, E-selectin, IL-1beta, TNF and transforming growth factor beta (TGF-beta) at light-microscope level, in cryostat sections of cerebral, cerebellar and brainstem tissues collected, post-mortem, from Ghanaian children. Among the 21 children investigated were 10 cases of CM, five of severe malarial anemia (SMA), one of purulent bacterial meningitis (PBM), two of non-central-nervous-system infection (NCNSI) and three children who had no infection (NI) when they died. Parasitised erythrocytes were detected in all of the sections from the cases of fatal malaria (CM and SMA), and sequestered leucocytes were present in most of the sections from the CM cases (but none of the sections from the SMA cases). Significantly elevated vascular expression of all three adhesion molecules investigated was detected in the brains of the 15 cases of fatal malaria and one of the cases of NCNSI (a child with Salmonella septicaemia), and in the malaria cases this showed highly significant co-localization with the areas of erythrocyte sequestration. In terms of the levels of expression of ICAM-1, VCAM-1 and E-selectin, there were, however, negligible differences between the CM and SMA cases. Although TGF-beta showed intravascular and perivascular distribution in all the subjects, its expression was most intense in the PBM case and the CM group. Only in the sections from the PBM and CM cases did TNF and IL-1beta show prominent brain parenchymal staining, in addition to the intravascular and perivascular staining seen in all subjects. The highest observed expression of each of the six antigens studied was in the cerebellar sections of the malaria cases. Endothelial activation in the brain therefore appears to be a feature of fatal malaria and Salmonella sepsis, and in cases of fatal malaria is closely associated with leucocyte sequestration. In the present study, IL-1beta and TNF were only up-regulated in the brains of children with neurodegenerative lesions, whereas TGF-beta was present in all cases.

Characterization and purification of acidocin CH5, a bacteriocin produced by Lactobacillus acidophilus CH5.

AIMS: To characterize and to purify a bacteriocin produced by Lactobacillus acidophilus strain with its activity restricted to Gram-positive bacteria. METHODS AND RESULTS: Native acidocin CH5, a bacteriocin produced by L. acidophilus CH5 an isolate from a dairy starter culture forms in MRS (Oxoid, Basingstoke, UK) broth high-molecular weight aggregates which can dissociate into smaller units (retained by 5 kDa membrane) with higher activity. Acidocin CH5 was purified using combinations of chromatographic methods based on hydrophobic and cation exchange principles and the N-terminal region was sequenced. CONCLUSIONS: Based on our results it is evident that acidocin CH5 belongs, according to bacteriocin classification, to the class II bacteriocins with identical N-terminal amino acid sequence described in the literature previously. SIGNIFICANCE AND IMPACT OF THE STUDY: The study has provided further data on bacteriocin acidocin CH5 from class II with wide spectrum of antimicrobial activity atypical for bacteriocins produced by L. acidophilus sharing the same homology.

Identification of surface-membrane P-type ATPases resembling fungal K(+)- and Na(+)-ATPases, in Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani.

Genomic DNA fragments encoding nine, novel, P-type ATPases in trypanosomatid organisms were amplified in PCR, using degenerate oligonucleotide primers that recognize the ATP-binding and -phosphorylation sites present in all P-type ATPases. Subsequent phylogenetic analysis, based on the presence of conserved motifs in predicted peptide sequences for six Trypanosoma brucei, T. cruzi or Leishmania donovani PCR fragments, identified calcium-, proton- and phospholipid-translocating ATPases. DNA fragments that predict proteins homologous to the fungal, type-IID, P-type, ATPase pumps that transport Na(+) or K(+) ions were also present in T. brucei (TBCA1; 1022 nucleotides representing 340 amino acids), T. cruzi (TCNA1; 1022 nucleotides representing 340 amino acids) and L. donovani (LDCA1; 1031 nucleotides representing 343 amino acids). Southern blots showed that the Na(+)-ATPases were each present as a single-copy gene. The LDCA1 fragment was used to clone the complete LDCA1 gene from an L. donovani genomic-DNA library. The LDCA1 gene encodes a protein, of 1047 amino acids, with a predicted molecular mass of 115,501 Da. The results of analyses based on northern blots and the rapid amplification of cDNA ends (RACE) indicated that LDCA1 was expressed in promastigotes and amastigotes from axenic cultures and in animal-derived amastigotes. TBCA1 was expressed, as a 5.0-kb transcript, in procyclic culture stages and bloodstream trypomastigotes, with the 5.0-kb message up-regulated six-fold in the trypomastigote stage. Western blots probed with an antibody to the partial TBCA1 peptide identified a 150-kDa protein that was detected, by immunofluorescence, on the surface membrane of procyclic T. brucei.

Antifungal activity of sodium acetate and Lactobacillus rhamnosus.

The inhibition of molds by sodium acetate in deMan Rogosa Sharpe (MRS) medium, along with the antifungal activity of Lactobacillus rhamnosus VT1, was studied by the slope agar plate method. MRS agar prepared with and without sodium acetate was used as the agar substrate. A total of 42 strains of Aspergillus, Penicillium, Fusarium, Alternaria, Cladosporium, and Rhizopus were used to compare sensitivities to the inhibitory activity of sodium acetate and L. rhamnosus VT1. It was found that sodium acetate in MRS medium affected the growth of 33 of the 42 mold strains tested to various degrees. The highest sensitivity to sodium acetate was shown by strains of Fusarium, followed by strains of Penicillium, Aspergillus, and Rhizopus. L. rhamnosus VT1 also inhibited mold growth. A significant finding was that sodium acetate and L. rhamnosus VT1 in combination exhibited a possible synergistic action. Thirty-nine of the 42 mold strains tested were completely inhibited by the presence of both antifungal agents. This finding confirms that sodium acetate, a basic component of commercial MRS medium, has strong antifungal properties, and this must be taken into consideration when evaluating the antifungal activity of Lactobacillus cultures grown in MRS broth.

Respiratory syncytial virus infection following hematopoietic stem cell transplantation.

Respiratory syncytial virus, one of the most common causes of respiratory infections in immunocompetent individuals, is frequently spread to recipients of HSCT by family members, other patients, and health care workers. In immunosuppressed individuals, progression from upper respiratory tract disease to pneumonia is common, and usually fatal if left untreated. We performed a retrospective analysis of RSV infections in recipients of autologous or allogeneic transplants. The incidence of RSV following allogeneic or autologous HSCT was 5.7% and 1.5%, respectively. Of the 58 patients with an RSV infection, 16 of 21 patients identified within the first post-transplant month, developed pneumonia. Seventy-two percent of patients received aerosolized ribavirin and/or RSV-IGIV, including 23 of 25 patients diagnosed with RSV pneumonia. In this aggressively treated patient population, three patients died of RSV disease, each following an unrelated HSCT.

Molecular markers for sex determination in papaya ( Carica papaya L.).

We have developed molecular markers tightly linked to Sex1, the gene that determines plant sex in papaya ( Carica papaya L.). Three RAPD products have been cloned and a portion of their DNA sequenced. Based on these sequences SCAR primers were synthesized. SCAR T12 and SCAR W11 produce products in hermaphrodite and male plants and only rarely in females. SCAR T1 produces a product in all papayas regardless of plant sex. SCAR T12 and SCAR W11 showed no recombination in a population of 182 F2 plants from a 'SunUp' by 'Kapoho' cross. Based on these results a PCR-based technique for rapidly and accurately determining the sex of papaya plants was developed using either W11 or T12 to detect the hermaphrodite or male allele and T1, which amplifies a product regardless of sex type, as a positive control. The sexing technique, using SCAR T12 and SCAR T1 as a positive control, was used to correctly predict hermaphrodite papaya plants in a population of seedlings with an overall accuracy of 99.2%.

The efficacy of 0.5% proparacaine stored at room temperature.

OBJECTIVE: To evaluate the efficacy of 0.5% proparacaine stored at room temperature for 6 weeks. ANIMALS STUDIED: Six normal dogs, evaluated on a weekly basis for 6 weeks. PROCEDURE: Proparacaine stored at 4 degrees C or at room temperature, was evaluated in the right and left eye of each dog, respectively. Corneal sensitivity was assessed with a Cochet-Bonnet aesthesiometer before and after instillation of proparacaine at each time point. RESULTS: A statistically significant difference was seen in corneal sensitivity beginning at week 3 for the eyes receiving room-temperature proparacaine compared to refrigerated proparacaine. Differences were not seen between right and left eyes before instillation of proparacaine for any time point, nor for eyes receiving refrigerated proparacaine over the 6 week study period. CONCLUSION: Short-term storage of proparacaine at room temperature did not affect efficacy, but storage at room temperature for more than 2 weeks resulted in a decrease in drug effect.

Benign outcome of RSV infection in children with cancer.

BACKGROUND: High case-fatality rates have been reported among adults who develop respiratory syncytial virus (RSV) infection while being treated for oncologic diseases, particularly after bone marrow transplantation. Previous reports of RSV infection among children with primary and acquired immunodeficiencies describe increased morbidity compared with that seen in immunocompetent children, but there have been few reports describing the outcome of RSV infection specifically among pediatric oncology patients. METHODS: We retrospectively reviewed the charts of all children being treated by the Pediatric Oncology Service at Memorial Sloan-Kettering Cancer Center who had positive tests for RSV between the Fall of 1994 and the Spring of 1998. Patients on the BMT Service were excluded from this analysis. RESULTS: Eighteen RSV infections were identified among pediatric oncology patients, who were being treated with aggressive, predominantly alkylator-based chemotherapy for a variety of oncologic diagnoses. Nine episodes of RSV infection (50%) were treated with specific antiviral therapy. Only one death less than 100 days from the diagnosis of RSV infection occurred among these 18 patients and was attributed to progressive leukemia. The remaining patients recovered fully, although three were readmitted with respiratory symptoms within two weeks of discharge. Seven patients had concurrent infection with other pathogenic organisms. CONCLUSIONS: In striking contrast with the outcome of RSV infection in adult oncology patients, there may be low mortality associated with RSV infection in pediatric oncology patients. It is possible that scheduled anti-neoplastic therapy need not be delayed for these patients when the diagnosis of RSV infection is made.

Improved memory functioning and frontal lobe maturation between childhood and adolescence: a structural MRI study.

Previous studies conducted by our group have provided evidence for age-related reductions in cortical thickness in dorsal frontal and parietal regions between childhood and adulthood, and gray matter volume increases of mesial temporal and anterior diencephalic structures. The purpose of this study was to describe neurobehavioral correlates of these brain maturational changes using morphometric analyses of brain magnetic resonance images (MRI) and two tests of cognitive abilities. Participants were 35 normal children roughly stratified by age (7 to 16 years) and sex (20 boys and 15 girls) and frontal and mesial temporal regions were anatomically defined in each subjects' MRI data. The California Verbal Learning Test-Children's Version and the Rey-Osterrieth Complex Figure test were used as measures of verbal and visuospatial memory and organizational abilities. Analyses designed to show regionally specific relationships between the brain and behavioral measures revealed interesting results. Specifically, frontal lobe gray matter thinning was more strongly predictive of delayed verbal memory functioning than was the mesial temporal lobe gray matter volume, and this relationship did not appear to be mediated by factors indexed in chronological age. Similar, but less regionally specific relationships were observed for measures of visuospatial memory abilities and frontal lobe maturation. Functional imaging studies in the literature consistently report activation in frontal regions in adults during retrieval tasks. The relationship between frontal lobe maturation and delayed recall observed here may be reflective of the children's development towards the more adult-like frontal lobe function revealed in the functional imaging studies.

Effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency.

OBJECTIVE: To determine effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency. ANIMALS: 32 cats. PROCEDURE: Renal mass was surgically reduced, and cats were assigned to 1 of 4 eight-cat groups. Group 1 received placebo, whereas groups 2, 3, and 4 received benazepril hydrochloride orally once daily for approximately 6.5 months at the following doses: group 2, 0.25 to 0.50 mg/kg of body weight; group 3, 0.50 to 1.00 mg/kg; and group 4, 1.00 to 2.00 mg/kg. Arterial blood pressures, glomerular filtration rate (GFR), and renal plasma flow were determined before treatment and during the treatment period. Other determinants of renal hemodynamics were measured by use of micropuncture techniques. Renal biopsy specimens were examined microscopically. RESULTS: Compared with cats that received placebo, mean systolic arterial blood pressure was significantly less and GFR significantly greater in cats that received benazepril. Glomerular capillary pressure and the ratio of efferent to afferent arteriolar vascular resistance were also significantly less in treated cats. However, histologic differences in renal specimens were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with benazepril sustained single nephron GFR in remnant nephrons of cats with induced renal insufficiency. Administration of benazepril was also associated with a small but significant reduction in degree of systemic hypertension and an increase in whole kidney GFR. Benazepril may be an effective treatment to slow the rate of progression of renal failure in cats with renal disease.

Trypanosoma brucei infection induces apoptosis and up-regulates neuroleukin expression in the cerebellum.

Human infection with Trypanosoma brucei may result in meningo-encephalitis, neuronal demyelination, blood-brain-barrier dysfunction, peri-vascular infiltration, astrocytosis and neuronal apoptosis. Prevention of the short- or long-term, parasite-induced, neuronal assault requires a better understanding of the host's responses to the infection at the molecular level. Northern analysis, cDNA micro-arrays, reverse-transcriptase-PCR (RT-PCR), SDS-PAGE and immunohistology were therefore used to investigate global gene and protein expression in the brains of mice infected with T. brucei. Temporal and spatial expression of neuroleukin (NLK), a predominant neurotrophin which is associated with neuronal protection and regeneration during neuronal assault in the brain, was then assessed. Expression of 20 of the 588 genes investigated (representing pro- and anti-inflammatory immuno-modulators, growth factors, neurotransmitters, and pro- and anti-apoptosis factors) was significantly altered (P < 0.05). TUNEL analysis revealed extensive apoptosis at peak parasitaemia, mainly in the cerebellum. RT-PCR analysis of two regulators of apoptosis, Bcl-x(L) (anti-apoptotic) and Bax (pro-apoptotic), revealed equivalent increases in levels of expression. NLK expression was up-regulated in punctated fashion in brain and was mainly localized to abnormal (stellate) catecholamine neurons (CN) in the locus coeruleus (LC) of infected [and, to a lesser degree, the normal (polygonal) cells of uninfected] brainstem. Expression of NLK receptor (NLK-R) was inversely correlated with that of NLK. At peak parasitaemia, trypanosome infection apparently induces cerebellar apoptosis and a corresponding increase in NLK expression. NLK may be modulating inflammation and is probably involved in protecting CN and the cerebellum against apoptosis.