Pulmonary hypertension: Spectrum of disease, clinical presentation and treatment outcomes at the main respiratory pulmonary hypertension clinic in KwaZulu-Natal Province, South Africa.

BACKGROUND: There are many causes of pulmonary hypertension (PH). However, the aetiology, management and treatment outcomes in South Africa (SA), which has a high burden of HIV, are lacking in the literature. OBJECTIVES: To characterise patient demographics, aetiology, clinical presentation and management of patients presenting to the only government-funded PH clinic in Durban, SA. METHODS: We retrospectively reviewed electronic charts of patients with confirmed PH who attended the respiratory PH clinic between 2011 and 2018. Demographic and clinical data, symptoms, pulmonary function testing, pulmonary artery pressure on echocardiography and treatment were analysed. Patients with group 2 PH were excluded from the present study as they were managed by cardiologists. RESULTS: We identified 93 patients with confirmed PH and the majority were female (82.8%; n=77). The majority of the patients were between the ages of 30 and 39 years at the time of diagnosis. Most patients were black African (64.5%; n=60), followed by Indians (26.9%; n=25) and whites (8.6%; n=8). The most common cause of PH was group 1 (75%; n=70), followed by group 4 (13%; n=12) and then group 3 (12%; n=11). HIV-associated PH accounted for 27% of all patients and was the main cause of PH in those classified in group 1 (38%; n=29). Two-thirds (66%) of patients were treated with sildenafil, the only treatment that was available. Patients on treatment showed significant improvement indicated by the World Health Organization functional class, mean 6-minute walk test and reduction in mean pulmonary artery pressure on echocardiography. CONCLUSION: HIV-associated PH is the most common cause of PH in SA. Sildenafil, the only drug available in our setting, is beneficial to most patients with PH.

How colipase-fatty acid interactions mediate adsorption of pancreatic lipase to interfaces.

Colipase is a cofactor protein which forms a 1:1 complex with pancreatic lipase. This facilitates lipase adsorption to phosphatidylcholine-rich interfaces, presumably as a consequence of the higher affinity of colipase for such interfaces. According to this model, the presence of colipase in an interface should be sufficient to enable lipase adsorption from the aqueous phase. To test this hypothesis, mixed monolayers of colipase, phosphatidylcholine, and fatty acid at the argon-buffer interface were exposed to lipase injected into the stirred aqueous subphase. Spread colipase remained associated with the lipid monolayer in a surface pressure- and lipid composition-dependent manner. For example, with diacylphosphatidylcholine alone, colipase remained in the lipid monolayer at surface pressures

Lateral packing of the pancreatic lipase cofactor, colipase, with phosphatidylcholine and substrates.

The interaction of the pancreatic lipase cofactor colipase with a diacylphosphatidylcholine, acylglycerols, and free fatty acid was investigated by monitoring its adsorption to monomolecular lipid films. Surface pressure and colipase surface concentration were measured as a function of the initial lipid concentration and composition. Colipase adsorbs to a level of 28-30 pmol/cm2 to form a close-packed monolayer of protein and interacts strongly with all lipids when the lipid chain:colipase ratio is 3, the triacylglycerol is excluded from the monolayer phase. Phosphatidylcholine, diacylglycerols, and free fatty acid remain in the monolayer phase up to 25 induces higher levels of colipase adsorption than at lower ratios. This suggests the formation of a novel structure involving fatty acid and/or colipase. Phosphatidylcholine also remains in the interface at lipid chain:colipase ratios >3 but shows little additional interaction with colipase. However, fluorescence microscopy suggests that the phosphatidylcholine and colipase are miscible in the interface. The specificity demonstrated in this study suggests that colipase may regulate the type of surfaces to which colipase and, hence, lipase bind and may control the species distribution of substrate to which bound lipase is exposed.

Specificity of the lipid-binding domain of apoC-II for the substrates and products of lipolysis.

Functional similarities between colipase and apolipoprotein C-II (apoC-II) in activating lipases suggest that apoC-II may, like colipase, preferentially interact with interfaces containing the substrates and products of lipolysis. To test this hypothesis, the binding of a peptide comprising residues of the cofactor implicated in lipid binding, apolipoprotein C-II(13-56), and, to a lesser extent, apoC-II, to monomolecular lipid films was characterized. The lipids used were a diacylphosphatidylcholine, a diacylglycerol, and a fatty acid. The peptide had an affinity for the argon-buffer interface and for all lipids consistent with a dissociation constant of <10 nM. Changes in surface pressure accompanying peptide binding were comparable to those reported for native apoC-II and indicate peptide miscibility with each of the lipids tested. The capacity of the surfaces to accommodate the peptide decreased with increasing lipid concentration in the interface, indicating competition between lipid and peptide for interfacial occupancy. At a lipid acyl chain density of 470 pmol/cm2, or 35 A2 per acyl chain, a lower limit of peptide adsorption was reached with all lipids. The limiting level of adsorption to phosphatidylcholine was only 1 pmol/cm2 compared with 6;-7 pmol/cm2 for fatty acid and diacylglycerol. Similar results were obtained with apoC-II. The difference in the extent of protein adsorption to lipid classes suggests that the distribution of apoC-II among lipoproteins will depend on their lipid composition and surface pressure.