Mosharraf H. Sarker

Quantitative assessment of medical waste generation in the capital city of Bangladesh

There is a concern that mismanagement of medical waste in developing countries may be a significant risk factor for disease transmission. Quantitative estimation of medical waste generation is needed to estimate the potential risk and as a basis for any waste management plan. Dhaka City, the capital of Bangladesh, is an example of a major city in a developing country where there has been no rigorous estimation of medical waste generation based upon a thorough scientific study. These estimates were obtained by stringent weighing of waste in a carefully chosen, representative, sample of HCEs, including non-residential diagnostic centres. This study used a statistically designed sampling of waste generation in a broad range of Health Care Establishments (HCEs) to indicate that the amount of waste produced in Dhaka can be estimated to be 37+/-5 ton per day. The proportion of this waste that would be classified as hazardous waste by World Health Organisation (WHO) guidelines was found to be approximately 21%. The amount of waste, and the proportion of hazardous waste, was found to vary significantly with the size and type of HCE.

Two components of blood‐brain barrier disruption in the rat

1 Permeability of pial venular capillaries to Lucifer Yellow (Ply) was measured using the single microvessel occlusion technique. 2 P ly was extremely low, when measured shortly after the removal of the meninges, consistent with an intact blood‐brain barrier, but rose spontaneously to (1.65 ± 060)× 10−6cms−1 (mean ±s.d.) within 20–‐60 min. This first phase of spontaneous disruption lasted 44–164 min. A second phase started when Ply rose sharply, and was characterized by rapid permeability fluctuations with a mean of (12.31 ± 15.14) × 1CT−6 cm s−1. 3 The first phase could be mimicked by applying the divalent cation ionophore A23187 in the presence of Ca2+, when Ply rose by (1.47±0–25) × 10−6 cm s−1 (mean±s.e.m.). Application of histamine (10 μm) to tight vessels increased Ply by (2.41 ± 0.22) × 10−6 cm s−1. 4 Substances that raised intraendothelial cAMP of vessels during the first phase of disruption reduced Ply to the initial blood‐brain barrier level. 5 The second phase could be prevented by applying catalase. Similar high and fluctuating Ply values could be produced reversibly by applying arachidonic acid or NH4C1. 6 This is the first report of two distinct types of permeability increase in the cerebral microvasculature, and reasons for this are discussed.

Acute effects of bradykinin on cerebral microvascular permeability in the anaesthetized rat

1 The permeability response to acutely applied bradykinin and [des‐Arg9]‐bradykinin on single cerebral venular capillaries has been investigated using the low molecular mass fluorescent dyes Lucifer Yellow and Sulforhodamine B with the single vessel occlusion technique. 2 When bradykinin was applied repeatedly for up to 2 h, the permeability increase was small and reversible for concentrations that ranged from 5 nm to 50 μm. 3 The logEC50 of the permeability response to bradykinin was −5.3 ± 0.15 (logm; mean ±s.e.m.). This was reduced to −6.37 ± 0.24 with the angiotensin‐converting enzyme inhibitor captopril, to −6.33 ± 0.19 with the neutral endopeptidase inhibitor phosphoramidon and to −7.3 ± 0.20 with captopril and phosphoramidon combined. 4 The permeability response to bradykinin was blocked by the bradykinin B2 receptor antagonist HOE 140, by inhibition of the Ca2+‐independent phospholipase A2, by the scavenging of free radicals, or by inhibition of both cyclo‐oxygenase and lipoxygenase in combination. Block of Ca2+ entry channels with SKF 96365 had no effect on the response. 5 Application of [des‐Arg9]‐bradykinin also increased permeability over the concentration range 5 nm to 50 μm, with a logEC50 of −5.6 ± 0.37. This response was not affected by free radical scavenging, but was completely blocked by the histamine H2 receptor blocker cimetidine. 6 These results imply that the acute permeability response to bradykinin is mediated via the release of arachidonic acid, which is acted on by cyclo‐oxygenase and lipoxygenase resulting in the formation of free radicals, and that the response to [des‐Arg9]‐bradykinin is mediated via histamine.

Regulation of cerebral microvascular permeability by histamine in the anaesthetized rat

1 The permeability response of slightly leaky pial venular capillaries to histamine was investigated using the single microvessel occlusion technique. 2 Histamine dose‐response curves showed that concentrations between 5 nm and 5 μM increased permeability, while concentrations from 50 μM to 5 mM reduced it. 3 The H2 receptor antagonist cimetidine (2 μM) blocked the effects of lower concentrations of histamine, while the H1 receptor antagonist mepyramine (3 nM) blocked those of higher concentrations of histamine. 4 The effects of lower doses of histamine were mimicked by the H2 receptor agonist dimaprit, and the effects of higher doses of histamine were mimicked by the H1 receptor agonist α‐2‐(2‐aminoethyl)pyridine (AEP). 5 Low concentrations of histamine, which normally increase the permeability of Lucifer Yellow (PLY), reduced it when co‐applied with the phosphodiesterase 4 (PDE4) inhibitor rolipram. Rolipram also potentiated the response to AEP, but had no effect on that to dimaprit. 6 The effects of dimaprit were blocked by reducing extracellular Ca2+ from 2.5 mM to nominally Ca2+ free, or by applying the calcium entry blocker SKF 96365.

Differential apicobasal VEGF signaling at vascular blood-neural barriers

Summary The vascular endothelium operates in a highly polarized environment, but to date there has been little exploration of apicobasal polarization of its signaling. We show that VEGF-A, histamine, IGFBP3, and LPA trigger unequal endothelial responses when acting from the circulation or the parenchymal side at blood-neural barriers. For VEGF-A, highly polarized receptor distribution contributed to distinct signaling patterns: VEGFR2, which was found to be predominantly abluminal, mediated increased permeability via p38; in contrast, luminal VEGFR1 led to Akt activation and facilitated cytoprotection. Importantly, such differential apicobasal signaling and VEGFR distribution were found in the microvasculature of brain and retina but not lung, indicating that endothelial cells at blood-neural barriers possess specialized signaling compartments that assign different functions depending on whether an agonist is tissue or blood borne.

The role of guanylyl cyclases in the permeability response to inflammatory mediators in pial venular capillaries in the rat

Inflammatory mediators have a role in the formation of cerebral oedema and there is evidence that cGMP is an important signal in vascular permeability increase. We have investigated the role and the source of cGMP in mediating the permeability response to acutely applied bradykinin and the histamine H2 agonist dimaprit on single cerebral venular capillaries, by using the single vessel occlusion technique. We found that 8‐bromo‐cGMP applied acutely resulted in a small and reversible permeability increase with a log EC50−7.2 ± 0.15 m. KT 5823, the inhibitor of cGMP‐dependent protein kinase, abolished the permeability responses to both bradykinin and dimaprit, while zaprinast, an inhibitor of type 5 phosphodiesterase, potentiated the response to bradykinin. On the other hand, l‐NMMA blocked the response to dimaprit, but not that to bradykinin. Inhibitors of soluble guanylyl cyclase, LY 85353 and methylene blue, also inhibited the permeability response to dimaprit, but not bradykinin. The permeability responses to the natriuretic peptides ANP and CNP were of similar magnitude to that of bradykinin with log EC50−10.0 ± 0.33 m and −8.7 ± 0.23 m, respectively. The natriuretic peptide receptor antagonist HS‐142–1 blocked permeability responses to bradykinin as well as to ANP, and leukotriene D4 blocked the responses to CNP and bradykinin, but not to dimaprit. In conclusion, the histamine H2 receptor appears to signal via cGMP that is generated by a NO and soluble guanylyl cyclase, while bradykinin B2 receptor also signals via cGMP but through particulate guanylyl cyclase.

Acute NADPH oxidase activation potentiates cerebrovascular permeability response to bradykinin in ischemia–reperfusion

Free radical generation is a key event in cerebral reperfusion injury. Bradykinin (Bk) and interleukin-1β (IL-1β) have both been implicated in edema formation after stroke, although acute Bk application itself results in only a modest permeability increase. We have investigated the molecular mechanism by assessing the permeability of single pial venules in a stroke model. Increased permeability on reperfusion was dependent on the duration of ischemia and was prevented by applying the B2 receptor antagonist HOE 140. Postreperfusion permeability increases were mimicked by applying Bk (5 μM) for 10 min and blocked by coapplying the IL-1 receptor antagonist with Bk. Furthermore, 10 min pretreatment with IL-1β resulted in a 3 orders of magnitude leftward shift of the acutely applied Bk concentration–response curve. The left shift was abolished by scavenging free radicals with superoxide dismutase and catalase. Apocynin coapplied with IL-1β completely blocked the potentiation, implying that NADPH oxidase assembly is the immediate target of IL-1β. In conclusion, this is first demonstration that bradykinin, released during cerebral ischemia, leads to IL-1β release, which in turn activates NADPH oxidase leading to blood–brain barrier breakdown.

An illicit economy: scavenging and recycling of medical waste.

This paper discusses a significant illicit economy, including black and grey aspects, associated with medical waste scavenging and recycling in a megacity, considering hazards to the specific group involved in scavenging as well as hazards to the general population of city dwellers. Data were collected in Dhaka, Bangladesh, using a variety of techniques based on formal representative sampling for fixed populations (such as recycling operatives) and adaptive sampling for roaming populations (such as scavengers). Extremely hazardous items (including date expired medicines, used syringes, knives, blades and saline bags) were scavenged, repackaged and resold to the community. Some HCE employees were also observed to sell hazardous items directly to scavengers, and both employees and scavengers were observed to supply contaminated items to an informal plastics recycling industry. This trade was made possible by the absence of segregation, secure storage and proper disposal of medical waste. Corruption, a lack of accountability and individual responsibility were also found to be contributors. In most cases the individuals involved with these activities did not understand the risks. Although motivation was often for personal gain or in support of substance abuse, participants sometimes felt that they were providing a useful service to the community.

Regulation of Cerebromicrovascular Permeability by Lysophosphatidic Acid

Microcirculation (2010) 17, 39–46. doi: 10.1111/j.1549‐8719.2010.001.x

Novel technique for estimating cerebrovascular permeability demonstrates capsazepine protection following ischemia-reperfusion

Objective: There has been some discussion as to whether the pial vasculature behaves in the same way as the blood‐brain barrier as a whole. Recent studies have shown that capsazepine protects these vessels from the effects of ischemia‐reperfusion. We have now used a new method to examine this protection in the whole brain.