In Vitro and in Vivo Study of a Photostable Quinone Compound with Enhanced Therapeutic Efficacy against Chagas Disease.

Chagas disease, a neglected tropical disease caused by the protozoan Trypanosoma cruzi poses a significant health challenge in rural areas of Latin America. The current pharmacological options exhibit notable side effects, demand prolonged administration, and display limited efficacy. Consequently, there is an urgent need to develop drugs that are safe and clinically effective. Previously, we identified a quinone compound (designated as compound 2) with potent antiprotozoal activity, based on the chemical structure of komaroviquinone, a natural product renowned for its antitrypanosomal effects. However, compound 2 was demonstrated considerably unstable to light. In this study, we elucidated the structure of the light-induced degradation products of compound 2 and probed the correlation between the quinone ring's substituents and its susceptibility to light. Our findings led to the discovery of quinones with significantly enhanced light stability, some of which exhibiting antitrypanosomal activity. The most promising compound was evaluated for drug efficacy in a mouse model of Chagas disease, revealing where a notable reduction in blood parasitemia.

Sub-acute combined degeneration of the spinal cord as first presentation of coeliac disease in a Sudanese child.

The prevalence of coeliac disease (CD) is rapidly rising in both developed and underdeveloped countries. CD classically presents with gastrointestinal manifestations, but it is now increasingly considered as a multisystem disease mostly affecting the central nervous system. Recently, a non-biopsy approach for the diagnosis of CD has been recommended by the European Society for paediatric gastroentrology, hepatology and nutrition. Here, we are reporting a 12-year-old Sudanese boy who presented with chronic diarrhoea and weight loss and lower limbs weakness. His examinations showed emaciation, pallor and weakness of both lower limbs and mixed upper and lower motor neuron signs and peripheral neuropathy, suggestive of sub-acute combined degeneration of the spinal cord (SACDSC). His initial investigations showed microcytic hypochromic anaemia with hypokalaemia and hypocalcaemia and very high titer of the IgA class of tissue transglutaminase (28× upper limit normal ) with a positive anti-endomeseal IgA antibodies. He was diagnosed with acute coeliac crisis with SACDSC, most likely due to Vitamin B12 deficiency. Although his initial cobalamine level was normal, he later developed macrocytosis and his neurological signs improved rapidly with injectable B12. We reported a rare neurological presentation of CD and we highlighted the non-biopsy approach for the diagnosis of CD in children.

Zinc level and effect of zinc supplementation on growth in a subset of Sudanese children with sickle cell disease.

A case-control interventional study was conducted to determine serum zinc levels in children with sickle cell disease (SCD) and to compare them to the levels in normal children and to the levels after 6 months of zinc supplementation. A total of 74 patients and 30 normal children, considered as controls for the zinc levels, were included. The clinical findings, including anthropometric measurements, were obtained. Serum zinc levels at the start and after 6 months, for the patients and at the start for the controls were measured. The mean age at enrolment and diagnosis were 7.5 ± 4.8 years and 5.5 ± 2.4 months, respectively. Male to female ratio was 1:1. Patients showed very low zinc levels at enrolment (0.268 ± 0.146 mg/l), while the controls had a mean zinc level at lower limits of normal (0.542 ± 0.087 mg/l) and a p-value of 0.04. After zinc supplementation, zinc levels in patients increased significantly with a p-value = 0.04. Zinc supplementation had positive effects on weight and height, with a p-value of 0.001 for both. The increase in body mass index and HC were not significant, with p-values of 0.058 and 0.067, respectively. Likewise, zinc supplementation had positive effects on the haematological indices as an increase in haemoglobin levels and a decrease of leucocyte counts, with p = 0.004 and 0.005, while the increase in platelet count was insignificant, p-value = 0.058. Furthermore, zinc supplementation decreased the frequency of hospitalisation significantly. We recommend considering zinc supplementation as one of the standard-of-care interventions in Sudanese children with SCD.

Is diabetic striatopathy the culprit of seizures in a patient with ketotic hyperglycemia-induced hemichorea-hemiballismus?

BACKGROUND: Diabetic striatopathy is a rare neurological manifestation of nonketotic hyperglycemia that presents with contralateral hemichorea-hemiballismus. Presentation with concurrent seizures is rarely reported. CLINICAL PRESENTATION: We report a case of diabetic striatopathy presenting with focal and generalized tonic-clonic seizures (GTCS) with right hemichorea-hemiballismus induced by a ketotic hyperglycemic state. Head MRI showed high T1-weighted signal intensity in the left lentiform nucleus with no significant diffusion restriction or postcontrast enhancement. The patient's condition gradually improved, with seizure control on AEDs. Hemichorea-hemiballismus significantly improved with adequate blood sugar control and resolved with low-dose haloperidol. CONCLUSIONS: Diabetic striatopathy presenting with hemichorea-hemiballismus and concurrent GTCS has been reported previously in two cases; however, it has never been reported in ketotic hyperglycemia. To the best of our knowledge, we herein report the first case report of focal and generalized seizures in a ketotic hyperglycemic state and mesial temporal sclerosis.

Breastfeeding associated hypernatraemia: clinical presentations, complications and outcome in a subset of Sudanese neonates.

A descriptive cross-sectional hospital-based study was conducted with the objectives to study clinical presentations, complications and outcomes of breastfeeding-associated hypernatraemia (BFAHN) in full-term neonates admitted to Ibrahim Malik Teaching Hospital, Khartoum, Sudan, during the period September 2017-2019. Eighty-four neonates with BFAHN were enrolled in the study. Collected demographic data of the neonates and their mothers included age at presentation, gender, birth weight, current weight, mode and place of delivery, maternal age, parity, education level, time of starting breastfeeding, presenting symptoms and signs, complications and outcome. The prevalence of the BFAHN was 15.5%. The mean age at presentation was 9.38 ± 5.95 days, range of 2-27 days and 59.5% were males. Most of them delivered vaginally (85.7%) and in hospital (63.1%). The mothers were multigravida in 58% and with a mean age of 28.14 ± 6.68 years and 3/4th of them started breastfeeding within the first hour. The most common symptoms and signs were fever, poor feeding, decreased urine output, jaundice, dehydration and loss of weight more than 10% of birth weight. The mortality rate was 21.4%. Complications included acute kidney injury in 82.1%, two patients needed peritoneal dialysis, one-third developed convulsions and two patients had intracranial bleeding. Factors associated with the development of the BFAHN were excessive loss of weight, multigravida, low maternal education level and vaginal delivery. Associated factors for death included thrombocytopenia, convulsions and severe hypernatraemia. Breast-milk sodium levels in mothers of 10 of the patients were high compared to 10 controls.

Clinical characteristics and needle aspiration management of Bacillus Calmette-Guérin lymphadenitis in children.

OBJECTIVES: To describe characteristics of children developing Bacillus Calmette-Guérin (BCG) lymphadenitis, and to evaluate needle aspiration treatment. METHODS: Children developing BCG lymphadenitis following BCG vaccination in Al-Rass General Hospital, Al-Rass, Saudi Arabia were prospectively studied from October 2008 to September 2013. Non-suppurative BCG lymphadenitis was conservatively managed, while suppurative lymphadenitis was treated by needle aspiration. RESULTS: The mean (SD) age of children (n=23) was 4.1 (1.4) months, and symptoms duration was 2.08 (1.38) months. Fifteen (65.2%) children had suppurative, whereas 8 (34.8%) had non-suppurative lymphadenitis. Age, gender, birth weight, and duration of symptoms were not significantly different between children with suppurative and non-suppurative lymphadenitis (p>0.05). Children with suppurative adenitis had higher weight, and larger size of the involved lymph nodes compared with those with non-suppurative nodes (p=0.001). Most (91.3%) had axillary lesions; with a mean lymph node size of 3.2 cm. Abscesses were detected by ultrasound in 8 (80%). Non-suppurative lymphadenitis was conservatively managed, while suppurative was aspirated. The mean duration for resolution was 3.25 months. Lymph nodes aspirate were positive for acid and alcohol fast bacilli in 10 patients (66.6%), and 3 of them grew Staphylococcus aureus. CONCLUSION: Bacillus Calmette-Guérin adenitis occurs in young children, mainly as unilocular suppurative left axillary group with a mean size of 3.2 cm. Needle aspiration is safe in treatment of suppurative lymphadenitis. Mycobacteria stained positive in most of the suppurative lesions. Excision is not needed.

Dying for milk: A neonate with severe hypernatremia associated with inadequate breast feeding.

Inadequate breastfeeding may result in malnutrition, hypernatremic dehydration and catastrophic outcomes. We describe a case of severe breast feeding associated hypernatremia which was complicated by acute seizures and severe hyperglycemia. The baby's condition was initially confused with neonatal diabetes mellitus.

Incomplete Kawasaki disease: The usefulness of BCG reactivation as a diagnostic tool.

Kawasaki disease (KD) is an extremely rare condition in infants younger than 3 months old. Cardiovascular complications are unfortunately most common in young infants and it is in this age group, incomplete Kawasaki disease (IKD) is more frequently reported. Because IKD is a diagnostic dilemma, any sign that could help early diagnosis, such as BCG reactivation is useful. Here we report on an infant less than 3 months old with IKD wherein, BCG reactivation helped us in making the diagnosis. In this article, we highlight the usefulness of this sign for early diagnosis of IKD, especially in countries where BCG vaccination is still part of the immunization schedule.

The neurology of carbonic anhydrase type II deficiency syndrome.

Carbonic anhydrase type II deficiency syndrome is an uncommon autosomal recessive disease with cardinal features including osteopetrosis, renal tubular acidosis and brain calcifications. We describe the neurological, neuro-ophthalmological and neuroradiological features of 23 individuals (10 males, 13 females; ages at final examination 2-29 years) from 10 unrelated consanguineous families with carbonic anhydrase type II deficiency syndrome due to homozygous intron 2 splice site mutation (the 'Arabic mutation'). All patients had osteopetrosis, renal tubular acidosis, developmental delay, short stature and craniofacial disproportion with large cranial vault and broad forehead. Mental retardation was present in approximately two-thirds and varied from mild to severe. General neurological examinations were unremarkable except for one patient with brisk deep tendon reflexes and two with severe mental retardation and spastic quadriparesis. Globes and retinae were normal, but optic nerve involvement was present in 23/46 eyes and was variable in severity, random in occurrence and statistically correlated with degree of optic canal narrowing. Ocular motility was full except for partial ductional limitations in two individuals. Saccadic abnormalities were present in two, while half of these patients had sensory or accommodative strabismus, and seven had congenital nystagmus. These abnormalities were most commonly associated with afferent disturbances, but a minor brainstem component to this disorder remains possible. All internal auditory canals were normal in size, and no patient had clinically significant hearing loss. Neuroimaging was performed in 18 patients and repeated over as long as 10 years. Brain calcification was generally progressive and followed a distinct distribution, involving predominantly basal ganglia and thalami and grey-white matter junction in frontal regions more than posterior regions. At least one child had no brain calcification at age 9 years, indicating that brain calcification may not always be present in carbonic anhydrase type II deficiency syndrome during childhood. Variability of brain calcification, cognitive disturbance and optic nerve involvement may imply additional genetic or epigenetic influences affecting the course of the disease. However, the overall phenotype of the disorder in this group of patients was somewhat less severe than reported previously, raising the possibility that early treatment of systemic acidosis with bicarbonate may be crucial in the outcome of this uncommon autosomal recessive problem.

Acute phase reactants in Sudanese children with severe protein-energy malnutrition.

The pre-dietary rehabilitation levels of acute phase proteins (APP) namely, alpha-1-antitrypsin (AAT), orosomucoid (ORO), haptoglobin (HAP), fibrinogen (FIB) and C-reactive protein (CRP) in the plasma of Sudanese children with severe protein energy malnutrition (PEM) were compared with those of normal controls, and with the levels after dietary rehabilitation. Eighty one children were included in the study; 49 with severe PEM (23 with marasmus, 17 with marasmic-kwashiorkor and 9 with kwashiorkor), 13 with tuberculosis (TB) and 19 healthy children as controls. The study showed a high incidence of infections, especially acute respiratory infection (ARI), diarrhoeal diseases and intestinal parasites in the malnourished children. The mean plasma level of albumin was significantly lower in the malnourished children compared to controls (P<0.001), with kwashiorkor children showing the lowest mean level. This hypoalbuminaemia was significantly associated with the presence of ARI and intestinal parasites. The mean plasma levels of the APP, except FIB, were significantly higher in malnourished children than in controls, with higher levels associated with ARI and the presence of fever. Malnourished children with TB had significantly higher mean levels of the APP (AAT, HAP, FIB, CRP) compared to those without TB. The mean levels of HAP and AAT were significantly lower in the presence of diarrhoea, suggesting their loss in the stool. The mean levels of the APP after two weeks dietary rehabilitation and antimicrobial treatment showed a significant drop in only two of the APP, namely CRP, ORO, while FIB showed a significant rise.

Infection and immunoglobulin levels in Sudanese children with severe protein-energy malnutrition.

A hospital-based case control study was carried out to determine the pattern of infections and immunoblobulin levels in Sudanese children with severe protein energy malnutrition (PEM). The pre-dietary rehabilitation levels of the three major immunoglobulins (IgG, IgA and IgM) were compared with those of normal controls, and with the levels after dietary rehabilitation. Eighty one children were included in the study: 49 with severe PEM (23 with marasmus, 17 with marasmic - kwashiorkor and 9 with kwashiorkor), 13 with tuberculosis and 19 healthy children as controls. The study showed high incidence of infections, especially pneumonia and gastrointestinal infections in the malnourished children. Of special concern was the high incidence of urinary tract infection: 13 (26.5%) had significant pyuria and 9 of them had positive urine cultures, mainly Escherichia coli. Eight of the malnourished children also had pulmonary TB, and the ESR and Mantoux tests were not helpful in the diagnosis. The Mantoux test was negative in 88.8% of the malnourished group compared to 62.5% in those malnourished with TB. The malnourished groups had significantly higher plasma levels of the 3 immunoglobulins. While the maramic group attained significantly higher levels of IgG and IgA compared to the marasmic -kwashiorkor and kwashiorkor groups, the 3 groups of PEM showed a uniformly higher level of the IgM. After 2 weeks of rehabilitation, the levels of the 3 immunoglobulins showed no significant changes, except for the IgA which significantly decreased in all malnourished and the oedematous groups, and the IgM which increased significantly in the oedematous group.