Changing use of surgical antibiotic prophylaxis in Thika Hospital, Kenya: a quality improvement intervention with an interrupted time series design.

INTRODUCTION: In low-income countries, Surgical Site Infection (SSI) is a common form of hospital-acquired infection. Antibiotic prophylaxis is an effective method of preventing these infections, if given immediately before the start of surgery. Although several studies in Africa have compared pre-operative versus post-operative prophylaxis, there are no studies describing the implementation of policies to improve prescribing of surgical antibiotic prophylaxis in African hospitals. METHODS: We conducted SSI surveillance at a typical Government hospital in Kenya over a 16 month period between August 2010 and December 2011, using standard definitions of SSI and the extent of contamination of surgical wounds. As an intervention, we developed a hospital policy that advised pre-operative antibiotic prophylaxis and discouraged extended post-operative antibiotics use. We measured process, outcome and balancing effects of this intervention in using an interrupted time series design. RESULTS: From a starting point of near-exclusive post-operative antibiotic use, after policy introduction in February 2011 there was rapid adoption of the use of pre-operative antibiotic prophylaxis (60% of operations at 1 week; 98% at 6 weeks) and a substantial decrease in the use of post-operative antibiotics (40% of operations at 1 week; 10% at 6 weeks) in Clean and Clean-Contaminated surgery. There was no immediate step-change in risk of SSI, but overall, there appeared to be a moderate reduction in the risk of superficial SSI across all levels of wound contamination. There were marked reductions in the costs associated with antibiotic use, the number of intravenous injections performed and nursing time spent administering these. CONCLUSION: Implementation of a locally developed policy regarding surgical antibiotic prophylaxis is an achievable quality improvement target for hospitals in low-income countries, and can lead to substantial benefits for individual patients and the institution.

Pyrenes and pyrendiones from Uvaria lucida.

A chemical investigation of the chloroform extract of the roots of Uvaria ludida Benth. (Annonaceae), an important African traditional medicine, led to the isolation of six new compounds; three pyrenes, 2-hydroxy-1,8-dimethoxypyrene (1), 8-methoxy-1,2-methylenedioxypyrene (2), and 7-hydroxy-8-methoxy-1,2-methylenedioxypyrene (3), two pyrenediones, 2-hydroxy-1,8-pyrenedione (4) and 2-methoxy-1,8-pyrenedione (5), and a sesquiterpene, (-)-10-oxo-isodauc-3-en-15-oic acid (6), together with eight known compounds (7-14). The structural elucidation by spectroscopic studies of the compounds isolated is described. While pyrenes did not exhibit strong cytotoxicity against human promyelocytic leukemia HL-60 cells, pyrenediones showed strong cytotoxicity. The IC(50) of 4 was 70 ng mL(-1), which was close to that of etoposide (IC(50) = 60 ng mL(-1)).

Chemical studies on the roots of Uvaria welwitschii.

A chemical investigation of the chloroform extract of the roots of Uvaria welwitschii (Annonaceae), an African traditional medicine taken for stomach ache, led to the isolation of eight new compounds, named welwitschins A-H (1-8), together with five known compounds (9-13). The structural elucidation by spectroscopic studies of the compounds isolated is described. All new compounds were flavonoids having a 2-hydroxy-3,4,6-trimethoxyphenyl moiety in the A-ring, and unsubstituted phenyl in the B-ring. Four of them (1-4) were monomeric flavonoids while the others (5-8) were dimeric flavonoids. The cytotoxicity of the isolated compounds against human promyelocytic leukemia HL-60 cells was investigated.

Hydroxyespintanol and schefflerichalcone: two new compounds from Uvaria scheffleri.

A chemical investigation of the petroleum ether extract and chloroform extract of the root of Uvaria scheffleri Diels (Annonaceae) led to the isolation of two new compounds, named hydroxyespintanol (1) and schefflerichalcone (2), together with eight known compounds (3-10). The structural elucidation of compounds 1 and 2 by spectroscopic studies is described. The cytotoxicity of the isolated compounds against human promyelocytic leukemia HL-60 cells was studied. Among these, 2'-hydroxy-3',4',6'-trimethoxychalcone (5) exhibited cytotoxicity (IC(50) 12 microM), and espintanol (3), which was the main ingredient, also showed some cytotoxicity (IC(50) 44 microM).

Antinociceptive effects of the extracts of Xylopia parviflora bark and its alkaloidal components in experimental animals.

In the present study, we attempted to elucidate the antinociceptive activity of Xylopia parviflora bark using the acetic acid-induced writhing test, hot plate test, and formalin test in mice. The MeOH extract (100 and 200 mg/kg, administered intraperitoneally (i.p.)) had an antinociceptive effect demonstrated by its inhibitory effects on writhing number induced by acetic acid. Three alkaloidal fractions exhibited significant antinociceptive effects in three animal models; the chloroform-soluble fraction, including secondary and tertiary alkaloids, exhibited the strongest effect. This result supported its use in folk medicine as an analgesic agent. We tested the main alkaloids of these fractions for their antinociceptive effects to clarify the active components. (+)-Corytuberine (6.3 and 12.5 mg/kg, i.p.) showed very strong activity, had a significant antinociceptive effect in the acetic acid-induced writhing test (with 49.4 and 98.9% reduction of writhes), in the hot plate test, and in the formalin test (with 55.4 and 90.6% inhibition during the first phase, and 73.9 and 99.9% during the second phase, respectively). (+)-Glaucine (12.5 and 25 mg/kg, i.p.) showed strong activity in three animal models, too. The activity of these compounds was also observed following oral administration in the acetic acid-induced writhing test.

Activation of micro, delta or kappa opioid receptors by DAMGO, DPDPE, U-50488 or U-69593 respectively causes antinociception in the formalin test in the naked mole-rat (Heterocephalus glaber).

Data available on the role of the opioid systems of the naked mole-rat in nociception is scanty and unique compared to that of other rodents. In the current study, the effect of DAMGO, DPDPE and U-50488 and U-69593 on formalin-induced (20 microl, 10%) nociception were investigated. Nociceptive-like behaviors were quantified by scoring in blocks of 5 min the total amount of time (s) the animal spent scratching/biting the injected paw in the early (0-5 min) and in the late (25-60 min) phase of the test. In both the early and late phases, administration of 1 or 5 mg/kg of DAMGO or DPDPE caused a naloxone-attenuated decrease in the mean scratching/biting time. U-50488 and U-69593 at all the doses tested did not significantly change the mean scratching/biting time in the early phase. However, in the late phase U-50488 or U-69593 at the highest doses tested (1 or 5 mg/kg or 0.025 or 0.05 mg/kg, respectively) caused a statistically significant and naloxone-attenuated decrease in the mean scratching/biting time. The data showed that mu, delta or kappa-selective opioids causes antinociception in the formalin test in this rodent, adding novel information on the role of opioid systems of the animal on pain regulation.

Stimulation of mu and delta opioid receptors induces hyperalgesia while stimulation of kappa receptors induces antinociception in the hot plate test in the naked mole-rat (Heterocephalus glaber).

The antinociceptive effects of highly selective mu (DAMGO), delta (DPDPE) and kappa (U-50488 and U-69593) opioid agonists were evaluated following intraperitoneal (i.p.) administration in the naked mole-rat. A hot plate test set at 60 degrees C was used as a nociceptive test and the latency to the stamping of the right hind paw (response latency) was used as the end-point. DAMGO (5-10 mg/kg) and DPDPE (2.5-5 mg/kg) caused a naloxone-reversible significant decrease in the mean response latency. Subcutaneous injection of naloxonazine (20 mg/kg) 24h prior to the administration of DAMGO (5 mg/kg) also blocked the reduction in the response latency observed when DAMGO was injected alone. On the contrary, U-50488 (2.5-5 mg/kg) or U-69593 (0.08 or 0.1 mg/kg) caused a naloxone-reversible significant increase in the mean response latency. These results showed that activation of mu or delta receptors caused hyperalgesia, whereas activation of kappa receptors caused antinociception in the hot plate test in naked mole-rat. This suggests that mu and delta receptors modulate thermal pain in a different way than kappa receptors in the naked mole-rat. It is not possible at the moment to point out how they modulate thermal pain as little is known about the neuropharmacology of the naked mole-rat.

Secondary and tertiary isoquinoline alkaloids from Xylopia parviflora.

From the secondary and tertiary alkaloidal fractions of the root and the bark of Xylopia parviflora (Annonaceae), the isoquinoline alkaloids, 10,11-dihydroxy-1,2-dimethoxynoraporphine and parvinine were isolated, along with 39 known alkaloids. Their structures were determined on the basis of analysis of spectroscopic data.

Quaternary isoquinoline alkaloids from Xylopia parviflora.

From the quaternary alkaloidal fraction of the bark and the root of Xylopia parviflora (Annonaceae), four isoquinoline alkaloids, xylopinidine, dehydrocoreximine, N, N-dimethylanomurine and N-methylphoebine were isolated along with the known compounds, pycnarrhine, lotusine, 6,7-dimethoxy-2-methyl-isoquinolinium salt, 1,2-dehydroreticuline, (-)-phellodendrine, (+)-tembetarine, (-)-litcubine, (+)-magnoflorine, tetradehydroreticuline, (-)-oblongine, (+)-menisperine, (+)-N-methylcorydine, stepharanine, (+)-xanthoplanine, dehydrodiscretine, jatrorrhizine and palmatine. 3,4-Dihydro-6,7-dimethoxy-2-methyl-isoquinolinium and N-methylpurpuerine were isolated as natural products for the first time. Their structures were determined on the basis of spectroscopic evidence.

Cytotoxic C-benzylated dihydrochalcones from Uvaria acuminata.

Two new C-benzylated dihydrochalcones, isochamuvaritin (1) and acumitin (2), have been isolated from the African medicinal plant Uvaria acuminata, together with the previously reported benzylbenzoate (3), uvaretin (4), isouvaretin (5), diuvaretin (6), and uvangoletin (7). The structural elucidation of compounds 1 and 2 in spectroscopic studies is described. C-Benzylated dihydrochalcones, especially 1, 2, 4, and 6, showed considerable cytotoxicity toward human promyelocytic leukemia HL-60 cells.