Health Science Reviews

by Masechaba Sebabatso Tsotetsi

Obesity and obesity-associated type 2 diabetes have emerged as two of the major threats to human health in the 21^stcentury. (1) In 2016 about 13% of the world’s adult population was obese. What’s even more shocking is the fact the prevalence of obesity is rapidly increasing in low- and middle-income countries where it used to be more prevalent in high-income countries. It was projected that by 2020 almost 1 in 10 children worldwide and 1 in 8 children in Africa will either be overweight or obese, which is quite worrying! Childhood obesity has been reported to be higher among South African Children. (2)

The consumption of an energy-rich, high-fat diet is known to trigger obesity and various metabolic changes including impaired glucose tolerance, insulin resistance and hyperglycemia. In this study the researchers wanted to investigate whether the deletion of the M₃ receptor gene could prevent or reduce the severity of these metabolic effects.

They found that consumption of a high-fat diet led to pronounced weight gain, hyperinsulinemia, impaired glucose tolerance and insulin resistance in the M3R wild-type mice but these metabolic deficits, induced by the consumption of the high-fat diet, were largely absent in the M3R knockout mice. They also observed that the M3R knockout mice maintained on a regular or high-fat diet consumed significantly less food than the M3R wild-type mice. Also, independent of the type of diet that the mice consumed, M3R knockout mice showed significantly increased rates of resting and total energy expenditure and locomotor activity. These results are shown in figure 1.

This paper shows that M3R knockout mice are largely protected against the detrimental effects metabolic deficits triggered by a high-fat diet, so the M₃ receptor may therefore represent a potential pharmacologic target for the treatment of obesity and associated metabolic disorders. So, there’s a bit of hope for the future.

References

1. Dinesh Gautam, Oksana Gavrilova, Jongrye Jeon, Stephanie Pack, William Jou, Yinghong Cui, Jian H. Li, and Ju¨rgen Wess (2006) Beneficial metabolic effects of M3 muscarinic acetylcholine receptor deficiency. Cell metabolism, 4(5), 363-375.
2. Olufunmilola Otitoola, Wilna Oldewage-Theron & Abdul Egal(2020) Prevalence of overweight and obesity among selected schoolchildren and adolescents in Cofimvaba, South Africa, South African Journal of Clinical Nutrition, DOI: 1080/16070658.2020.1733305

This technique measured all the genes expressed by each individual T cells. Based on the genes each T cell expressed, they were able to group cells expressing similar genes into clusters of either Treg cells or memory T cells (Tmem – antigen experienced T cells) as shown in the Figure 1. Further examination of these cell clusters revealed high diversity of Treg cell populations within the NLT and LT.

Pseudotime ordering analysis,  an analysis that estimates the distance between cell transition states, was used to determine the trajectory of the Treg cells. Using this analysis ,transcriptomic adaptations occurring in Treg cells during their transition from the lymph node to non-lymphoid tissues could identify Treg cell subpopulations aligning in a continuous trajectory as shown in figure 2  and diverging towards their specific tissue fates carrying their respective address book e.g  branchial lymph node (bLN) Treg  (Lef1, Tcf7, Sell),  mesenteric lymph node (mLN) Treg (Nfil3, Ccr8, Cxcr6, Gzmb), skin Treg (Sell, Tcf7, Rora and Tnfrsf9), and colon Treg (Sell, Tcf7, Rora and Tnfrsf9). These finding provide an easy tool to determine the fate of Treg cells in circulation and also demonstrated that the adaptation of Treg cells migrating to skin or colon depend on a shared transcriptional trajectory.

Using a melanoma mouse model, they could also show that, the core identity of NLT Treg cells is conserved between mouse and human. This genomic approach reveals a dynamic adaptation of T cells as they traffic across tissues and provide an open resource for investigating in vivo CD4+ T cell phenotypes in mouse and human, to ultimately harness NLT CD4 T cells as future therapeutic target.

REFERENCE

Miragaia, R. J. et al. (2019) ‘Single-Cell Transcriptomic of Regulatory T Cells Reveals Trajectories of Tissue Adaptation Resource Single-Cell’, pp. 493–504. doi: 10.1016/j.immuni.2019.01.001

 

By Jodie Jacobs

A question on the rise is whether HIV has a direct correlation on cardiovascular disease.  The emerging prevalence of cardiovascular diseases (CVD) present in HIV-infected patients is particularly interesting. People infected with HIV who die from cardiovascular complications is rising in comparison to people who die as a result of the virus itself. So, what does this mean?  Testing individuals who are HIV-positive for heart diseases and defects will help improve treatment and management regimes for those suffering from both diseases. In turn, this will lower the death rate caused by the world’s leading cause of death, cardiovascular disease. In this particular study, researchers investigated the prevalence and range of heart diseases in children in the Pediatric Infectious Disease clinic at Mulago Hospital in Sub-Saharan Africa where more than 50% of the world’s HIV-infected individuals reside.

Using imaging techniques, 230 children (112 males and 118 females) were examined where 13.9% had asymptomatic HIV, 67.8% had AIDS related complex and 18.3% had AIDS. Any structural defects relating to congenital heart disease, dimensions of heart chambers during relaxation and expansion, function of left ventricle, valve function and direction of blood flow were examined.

Of the 230 patients, 81.7% of patients were symptomatic for HIV while 18.3% were asymptomatic. The range of heart defects detected included Left ventricular systolic dysfunction (failure of heart to pump sufficient blood), right ventricular dilatation (chamber enlargement), pericardial effusion (excess fluid in pericardial cavity), congenital heart disease, dilated cardiomyopathy (ineffective pumping of blood), right and left  ventricular hypertrophy (thickening of heart wall), partial right bundle branch block and sinus tachycardia (elevated heart rhythm) with sinus tachycardia (25.53%) and left ventricular systolic dysfunction (21.28%) being the most significant. Only 5 children presented with cardiac abnormalities prior to the investigation. Other abnormalities included atrial septal defect (hole in the heart wall between two chambers) and mitral valve disease (partially functioning mitral valve).

Now the question would be what is the link between the two? Well, this study looked at the development and signs of heart defects in HIV-positive children who had no previous signs or complications. Cardiovascular abnormalities such as sinus tachycardia and left ventricular systolic dysfunction were found to be most prevalent in children with AIDS compare to those with ARC and who were asymptomatic. The direct effect which HIV has on cardiac abnormality development is yet to be established but a famous theory includes the role HIV plays in immune activation and inflammation that contributes to CVD risk and abnormalities. Countries in Sub-Saharan Africa where HIV is highly prevalent appears to increase the prevalence of cardiac abnormalities which may increase mortality rate. So, it is recommended that children suffering from HIV and ARC should be screened for any cardiovascular abnormalities as it will assist in effective treatment procedures and disease management.

Reference

Lubega S, Zirembuzi GW, Lwabi P. 2005. Heart disease among children with HIV/AIDS attending the paediatric infectious disease clinic at Mulago Hospital. African health sciences, 5(3): 219-226.

by Noluthando Magubane

Carpal tunnel syndrome (CTS) is the most common median nerve neuropathy that was first described by Paget in 1854. It is a medical condition caused by damage to the median nerve due to compression and traction of the nerve at the level of the carpal tunnel. This condition affects 4-5% of the population and is most prevalent in females around the ages of 40-60 but males are also susceptible to this condition (average age of 45-60). It is characterised by pain, numbness or a tingling sensation in the affected hand and arm.

The carpal tunnel is an osteofibrous outlet lying between the transverse carpal ligament (the intermediate part of a fibrous connective tissue band called the flexor retinaculum) which forms the roof, and the carpal bones that form the floor of the tunnel. Entering through the tunnel are nine flexor tendons and the median nerve. The median nerve enters the tunnel through the midline of or slightly radial (closer to the thumb) and innervates the first three radial digits and the radial half of the 4^th digit, it also gives off a palmer sensory cutaneous branch which innervates the cutaneous skin of the palm these are the areas affected in CTS.

The pathophysiology of carpal tunnel syndrome involves an increased pressure within the carpal tunnel that decreases the function of the median nerve. Conditions that lead to compression of the carpal tunnel and hinders mobility, create lesions on the median nerve when the wrist is moved. Hypertrophy of the synovial tissue of the flexor tendons is a possible cause, in this condition constructive scar tissue is formed around the median nerve compressing it and increasing the pressure around the nerve resulting in tearing. The issue causing CTS could also originate at the nerve itself when the connective tissue surround the nerve becomes stiff. The purpose of this connective tissue is for the nerve to be extendable and not become injured when the wrist is moved. The stiffness exposes the nerve to shearing forces that could harm the nerve.

Risk factors associated with CTS can be medical or occupational. Medical factors include extrinsic factors such a fracture in the distal radius that increase the volume of the synovial sheath within the tunnel, intrinsic factors where tumours form in the tunnel increasing the occupied volume and neuropathic factors such as diabetes or alcoholism that can affect the function of the median nerve. Occupational risk factors involve any repetitive wrist movement or repetitive tasks such as typing. CTS can be treated by resting the affected hand and surgical interventions are also possible.

Reference

Aboonq, M. (2015) Pathophysiology of carpal tunnel syndrome. Neurosciences. 20 (1), 4–9.

by Sithandiwe Dlamini 

According to the South African Demographic and Health Survey 2016, 68% of women and 39% of men aged 15 and older were overweight or obese. According to the World Health Organisation 2016, 39% of adults aged 18 and over were overweight, while 13% were obese. This is significant as obesity contributes to diseases such as diabetes. It’s development is influenced by lifestyle (diet, physical inactivity), family history and genetic predisposition.

However, the gut microbiome is very likely to play an important role as the development of obesity-related disorders are strongly linked to the human gut microbiome. More specifically, the bacterium Akkermansia muciniphila has interested researchers. Why A. muciniphila? In rodents treated with this bacterium, there was a reduction in obesity and related disorders such as insulin resistance and glucose intolerance. However, its administration and effects had never been investigated in humans.

Recently, an exploratory, proof of concept study in the form of a randomised, double-blind placebo-controlled pilot study was done in overweight/obese, insulin-resistant participants. This was for the supplementation of A. muciniphila in humans. The participants were randomised to either receive the placebo, live or pasteurized A. muciniphila for 3 months, while maintaining their normal diet and physical activity. Metabolic parameters such as insulin sensitivity and insulin resistance were measured.

 

As seen in the graphs above, live and pasteurized A. muciniphila significantly reduced insulin resistance by reducing the insulin resistance score while pasteurized A. muciniphila significantly improved the insulin sensitivity index.

The above study showed that supplementation with A. muciniphila improved insulin sensitivity and insulin resistance Improvement in these metabolic parameters was associated with the impact of supplementation on body weight, fat mass and hip circumference. The study shows that A. muciniphila can be administered to humans and is safe. It provides the foundation for further clinical research with larger sample sizes and more standardized and accurate ways of measurement. It has the potential use for future clinical interventions for obesity-related disorders in conjunction with lifestyle interventions. A patent has been registered for the use of A. muciniphila in treating metabolic conditions, proving its utility as a therapeutic

References:

Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017;23(1):107–13.

Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva Set al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nature Medicine.2019;25(7):1096-1103.

Cani P, Everard A, Belzer C, de Vos WM. Use of Akkermansia for treating metabolic disorders field. Belgium; PCT/EP2012/073011, 2014.