CASE SERIES: Here, we reported five cases of this disorder with different clinical presentations from two tertiary hospitals in Kelantan state, Malaysia within a two year-period. Most of them were elderly, except for one who presented at the age of 36 years old. No direct or secondary cause was identified except for one patient who had developed from pregnancy-related at 3 weeks postpartum. These patients presented with spontaneous bleeding typically into skin, muscles, and mucous membranes but also at rare site in the epidural space. All patients denied previous history of bleeding or family history of bleeding disorder. FVIII activities were recorded between <1% to 19%, while the inhibitor titre levels were between 3.9 BU to 340 BU. The treatment approaches especially at presentation were complicated by unfamiliarity of managing this rare condition but all these patients received appropriate medical attention.

RESULTS: None of the goats showed clinical signs or gross lesions. The most consistent histopathology finding was the infiltration of mononuclear cells, chiefly the macrophages with few lymphocytes and occasionally neutrophils in all organs along the urinary tract of the infected goats of Group 2. Other histopathology findings included mild necrosis of the epithelial cells of the renal tubules, congestion and occasional haemorrhages in the various tissues. Kidneys showed the most severe lesions. Immunoperoxidase staining revealed the presence of B. melitensis within the infiltrating macrophages and the epithelium of renal tubules, ureter, urethra and urinary bladder. Most extensive distribution was observed in the urinary bladder. Brucella melitensis was successfully isolated at low concentration (3.4 × 103 cfu/g) in the various organs of the urinary tract and at high concentration (2.4 × 108 cfu/mL) in the vaginal swabs of all infected goats. Although B. melitensis was successfully isolated from the various organs of the urinary tract, it was not isolated from the urine samples that were collected from the urinary bladder at necropsy.

OBJECTIVE: To describe the pathological changes, identification and distribution of B. melitensis in foetuses of experimentally infected does.

METHODS: Twelve female goats of approximately 90 days pregnant were divided into 4 groups. Group 1 was exposed intra-conjunctival to 100 µL of sterile PBS while goats of Groups 2, 3 and 4 were similarly exposed to 100 µL of an inoculum containing 109 CFU/mL of live B. melitensis. Goats of these groups were killed at 15, 30 and 60 days post-inoculation, respectively. Foetal fluid and tissues were collected for bacterial identification (using direct bacterial culture, PCR and immuno-peroxidase staining) and histopathological examination.

RESULTS: Bilateral intra-conjunctival exposure of pregnant does resulted in in-utero infection of the foetuses. All full-term foetuses of group 4 were either aborted or stillborn, showing petechiations of the skin or absence of hair coat with subcutaneous oedema. The internal organs showed most severe lesions. Immune-peroxidase staining revealed antigen distribution in all organs that became most extensive in group 4. Brucella melitensis was successfully isolated from the stomach content, foetal fluid and various other organs.

METHODS: Pregnant rats were divided into three groups: control, stress, and stress treated with Tualang honey. The stress and stress treated with Tualang honey groups were subjected to restraint stress from day 11 of pregnancy until delivery. Ten week old male offspring (n = 9 from each group) were given formalin injection and their nociceptive behaviours were recorded. After 2 h, the rats were sacrificed, and their spinal cords were removed to assess oxidative stress activity and morphology. Nociceptive behaviour was analysed using repeated measures analysis of variance (ANOVA), while the levels of oxidative stress parameters and number of Nissl-stained neurons were analysed using a one-way ANOVA.

RESULTS: This study demonstrated that prenatal stress was associated with increased nociceptive behaviour, changes in the oxidative stress parameters and morphology of the spinal cord of offspring exposed to prenatal stress; administration of Tualang honey reduced the alteration of these parameters.