Stimulation of the occipital nerve for the treatment of migraine: current state and future prospects.

Migraine is a common disabling malady. Despite the development of therapeutic agents such as the triptans, a significant number of patients continue to suffer. The evolution of peripheral nerve stimulation for headache management, may significantly improve the management of those who suffer from moderate to refractory migraine symptoms.

Annojahnin from Annona jahnii: a possible precursor of mono-tetrahydrofuran acetogenins.

A new cytotoxic Annonaceous acetogenin, annojahnin (1), was isolated from the twigs of Annona jahnii (Annonaceae) by bioactivity-directed fractionation using lethality to brine shrimp. Compound 1 represents an unusual type of C-37 Annonaceous acetogenin, lacking either tetrahydrofuran (THF) or epoxide rings, bearing a keto group at C-10, and possessing a double bond located two methylenes away from a vicinal diol. The structure and absolute configuration of 1 were elucidated by 1H and 13C NMR, COSY, and single-relayed COSY and from chemical derivatives. 4-Deoxy-18/21-trans-annomontacin 10-one (4) and 4-deoxy-18/21-cis-annomontacin-10-one (5), two semisynthetic mono-THF acetogenins, were prepared from 1 by reactions that mimic the biogenetic pathways. These acetogenins showed selective cytotoxicities, comparable or superior to adriamycin, among six human solid tumor cell lines. Reduction of the 10-keto of 1, to the racemic 10-OH derivative (3), retained the bioactivities as did the conversion of 1 to 4 and 5.

Muricoreacin and murihexocin C, mono-tetrahydrofuran acetogenins, from the leaves of Annona muricata.

Bioactivity-directed fractionation of the leaves of Annona muricata L. (Annonaceae) resulted in the isolation of two new Annonaceous acetogenins, muricoreacin (1) and murihexocin C (2). Compounds 1 and 2 showed significant cytotoxicities among six human tumor cell lines with selectivities to the prostate adenocarcinoma (PC-3) and pancreatic carcinoma (PACA-2) cell lines.

Glabracins A and B, two new acetogenins from Annona glabra.

Two new bioactive bis-THF Annonaceous acetogenins, glabracins A (1) and B (2), and two previously known acetogenins, javoricin (3) and bullatanocin (4), have been isolated from the leaves of Annona glabra by activity-directed fractionation using the brine shrimp lethality test (BST). The structures of 1 and 2 were elucidated based on spectroscopic and chemical methods, and the absolute stereochemistries were partially determined by the advanced Mosher ester method. 1 and 2 showed selective cytotoxicities to certain human tumor cell lines, and 1 was significantly more potent although 1 and 2 differ only in the stereochemistry of their vicinal diols at C-23/24.

Cytotoxic and insecticidal constituents of the unripe fruit of Persea americana.

Unripe avocado fruit (Persea americana) was subjected to a bioactivity-directed fractionation, as monitored via the brine shrimp lethality assay, to isolate three major bioactive constituents (1-3). Compounds 1-3 all have a 1,2,4-triol moiety and a long aliphatic chain that terminates as either an alkane, alkene, or alkyne, respectively; 1 is new, while 2 and 3 have been described previously but not as cytotoxic or pesticidal agents. All have activity against six human tumor cell lines in culture and show selectivity for human prostate adenocarcinoma (PC-3) cells with 3 being nearly as potent as adriamycin. Also, when tested against yellow fever mosquito larva, 3 was more effective than rotenone, a natural botanical insecticide and positive control.

Two new mono-tetrahydrofuran ring acetogenins, annomuricin E and muricapentocin, from the leaves of Annona muricata.

Bioactivity-directed fractionation of the leaf extract of Annona muricata L. (Annonaceae) has resulted in the isolation of two new Annonaceous acetogenins, annomuricine (1) and muricapentocin (2). Compounds 1 and 2 are monotetrahydrofuran ring acetogenins bearing two flanking hydroxyl groups; however, each has three additional hydroxyl groups. Compound 1 has an erythro 1,2-diol, and 2 has a 1,5,9-triol moiety. Both 1 and 2 showed significant cytotoxicities against six types of human tumors, with selectivities to the pancreatic carcinoma (PACA-2) and colon adenocarcinoma (HT-29) cell lines.

New bioactive triterpenoids from Melia volkensii.

Bioactivity-directed fractionation of the root bark of Melia volkensii resulted in the isolation of two new natural products, meliavolkinin (1) and melianin C (3), together with two known compounds, 1,3-diacetylvilasinin (2) and melianin B (4). Jones oxidation of 4 gave compounds 3, 23,24-diketomelianin B (5), and 16,23,24-triketomelianin B (6). The structures of the new compounds were elucidated by spectral and chemical data. Compounds 1-6 all showed marginal cytotoxicities against certain human tumor cell lines, while 5 showed selective cytotoxicities for the human prostate (PC-3) and pancreatic (PACA-2) cell lines with potencies comparable to those of adriamycin.

Finite element analysis in the design and characterization of an absorbable cement restrictor.

The benefit of using a cement restrictor to achieve cement pressurization during total hip arthroplasty is well established. An absorbable cement restrictor design has been developed with the use of a finite element model. The non-linear axisymmetric model was used to optimize specific parameters so as to perform within acceptable limits when tested over a specified range of medullary canal sizes. The results achieved from a hybrid experimental/analytical design methodology allowed for a shorter development cycle for the initial size and each additional size in the design family thereafter. The resulting cement restrictor design was compared to and exceeded the performance of currently clinically accepted devices in resisting migration.

Weights and hematology of wild black bears during hibernation.

We compared weights and hematological profiles of adult (greater than 3-yr-old) female black bears (Ursus americanus) during hibernation (after 8 January). We handled 28 bears one to four times (total of 47) over 4 yr of varying mast and berry production. Mean weight of lactating bears was greater (P less than 0.0001) than that of non-lactating females. White blood cells (P less than 0.05) and mean corpuscular volume (P = 0.005) also differed between lactating and non-lactating bears. Hemoglobin (P = 0.006) and mean corpuscular hemoglobin concentration (P = 0.02) varied among years; values were lowest during 1975, following decreased precipitation and the occurrence of a second year of mast and berry crop shortages in a three-year period. Significant (P less than 0.05) interaction between reproductive status (lactating versus non-lactating) and study year for hemoglobin, red blood cells, and packed cell volume, and increased mean corpuscular volume, suggested a greater nutritional challenge for lactating females compared to non-lactating females during the 1975 denning season. Our data suggest that hematological characteristics of denning bears may be more sensitive than weights as indicators of annual changes in nutritional status; however, other influential factors, in addition to mast and berry crop production, remain to be examined.

Mechanical visceral pain model: chronic intermittent intestinal distention in the rat.

Animal models designed to test the effectiveness of analgesic agents against viceral pain typically rely on a noxious chemical irritation of the peritoneum, e.g., acetic acid and phenylquinone writhing tests. While useful, this type of assay depends upon an acute inflammation and the release of local alogens. Further, ethical and scientific constraints prevent repeated assessments in a single animal, thereby compounding the difficulty of assessing tolerance development to analgesic agents. To overcome these constraints we developed a model for mechanical visceral pain (VPM) based on a repeatable and reversible duodenal distention in the rat. A chronic indwelling intraduodenal balloon catheter is well tolerated and upon inflation produces a writhing response graded in proportion to distention. This response is inhibited by morphine in a dose dependent manner.

Effect of specimen size on work-of-fracture measurements.

It has been suggested that work-of-fracture, which quantifies the ability of a material to resist fracture, is dependent on specimen size. This experiment compared work-of-fracture, calculated as energy per unit area, for different specimen sizes of Plexiglas, bovine tibial bone and aluminum. Three different geometrically similar cross sections were tested for each material for a total of 54 specimens. Work-of-fracture was measured by loading a notched beam (triangular cross section) in three-point bending at a constant deformation rate. The energy necessary to cause fracture was measured from a load-deformation curve. Specimen fracture area was determined using macrophotography. Atomic absorption spectrophotometry was used to determine weight percent calcium of bone specimens and quantitative light microscopy was used to determine fractional void area. Analysis of variance showed no effect of specimen size on work-of-fracture for aluminum or Plexiglas specimens (p greater than 0.05). A significant difference was found, however, between the large (area = 11.7 +/- 1.9 mm2) and small (area = 3.48 +/- 0.68 mm2) bone specimens and between the medium (area = 5.89 +/- 0.69 mm2) and small (area = 3.48 +/- 0.68 mm2) bone specimens. No correlation was found between work-of-fracture and either calcium content (r2 = 0.128) or fractional void area (r2 = 0.0713). The mean work-of-fracture values found are as follows: aluminum, 59.8 +/- 13.7 kJ m-2; Plexiglas, 0.620 +/- 0.074 kJ m-2; bone (area 5.89 +/- 0.69 mm2-11.7 +/- 1.9 mm2), 9.72 +/- 1.93 kJ m-2 and bone (area 3.48 +/- 0.68 mm2), 5.48 +/- 1.79 kJ m-2.

Clostridial myonecrosis in a black bear associated with drug administration.

Clostridial myonecrosis is described for the first time in a black bear (Ursus americanus). This fatal condition appeared within three days following immobilization with parenterally administered promazine hydrochloride and phencyclidine hydrochloride. Clostridial myonecrosis may be responsible for other unexplained deaths of animals following recovery from immobilizing drugs. Administration of prophylactic antibiotics to immobilized animals might be considered.

Parasites of black bears of the Lake Superior region.

Parasites collected from free-ranging black bears, Ursus americanus Pallas, 1780, from northeastern Minnesota or northern Michigan include the dog tick, Dermacentor variabilis (Say, 1821), the winter tick, D. ALBIPICTUS (Packard, 1869), a louse, Trichodectes pinguis euarctidoes Hopkins, 1954, an ascarid worm, Baylisascaris transfuga (rudolphi, 1819), a filarial worm, Dirofilaria ursi Yamaguti, 1941, taeniid tapeworms, and unidentified fleas. The broad fish tapeworm, Diphyllobothrium latum (linnaeus, 1785), was reported to be common in man and black bears in northeastern Minnesota earlier in this century, but now it apparently is uncommon in black bears in norther Wisconsin. Cannibalism of carcasses is common in the black bear and may play a major role in the transmission of Trichinella.