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Biomedical subjects

M Pink

Publications and source records attributed to M Pink.

At least 19 recordsLinked to original sources
PubMed2001

Three-coordinate copper(II)-phenolate complexes.

The reactions of LCuCl (L = 2,4-bis((2,6-diisopropylphenyl)imido)pentane (L(iPr)), 2,4-bis((2,6-diisopropylphenyl)imido)-3-chloropentane (L(CliPr))) with the phenolates TlOAr (Ar = C(6)H(3)Me(2), C(6)H(4)OMe, C(6)H(4)tBu) and NaOC(6)H(3)(tBu)(2) were explored. Novel three-coordinate Cu(II)-phenolates, LCuOAr, were isolated from the reactions with the thallium phenolates and were characterized by X-ray crystallography and spectroscopy (UV-vis, EPR). The complexes feature short Cu-O(phenolate) distances (average Cu-O = 1.81 A) and, with one exception, irregular N-Cu-O(phenolate) angles that differ within each compound (15 degrees < Delta < 28 degrees, where Delta = angleN(1)-Cu-O - angleN(2)-Cu-O). The exception is L(iPr)Cu(OC(6)H(4)tBu), for which X-ray structures at -100 and 25 degrees C differed due to an unusual reversible phase change with nonmerohedral twinning (2:1 ratio) in the low-temperature form. The high-temperature form has local C(2)(v) symmetry (Delta = 0 degrees ), and upon cooling below the phase transition temperature (-8 +/- 5 degrees C) lateral movement of the phenolate ligand (Delta = 17.6 degrees ) and rotation of the phenolate plane by 10.7 degrees occurs. Resonance Raman spectroscopic data acquired for L(iPr)Cu(OC(6)H(4)tBu) corroborated assignment of phenolate --> Cu(II) LMCT character in the UV-vis spectra. Cyclic voltammetry experiments (THF, 0.5 M NBu(4)PF(6)) revealed negative E(1/2) values for the Cu(II)/Cu(I) couples relative to NHE, consistent with enhanced stabilization of the Cu(II) state by both the strongly electron donating beta-diketiminate ligand and the phenolates. Although thermally stable, the Cu(II)-phenolates are unusually reactive with dioxygen, albeit to give product(s) that have yet to be identified. In the reaction of L(iPr)CuCl with NaOC(6)H(3)(tBu)(2) no Cu(II)-phenolate was observed. Instead, a Cu(I) complex was generated quantitatively by trapping with added isocyanide, [L(iPr)CuNC(C(6)H(3)Me(2))], along with 3,3',5,5'-tetra-tert-butyl-4,4'-dibenzoquinone and 2,6-di-tert-butylphenol in 27 +/- 3% and 46 +/- 6% yields, respectively, corresponding to the overall reaction 4L(iPr)Cu(II)Cl + 4NaOAr --> 4L(iPr)Cu(I) + 4NaCl + dibenzoquinone + 2(phenol).

Catalysis↗
PubMed2001

Macrocyclic metalloenediynes of Cu(II) and Zn(II): a thermal reactivity comparison.

The syntheses of tetradentate enediyne macrocycles with 24 (tact1:1)-, 26 (tact1:2)-, and 28 (tact2:2)-membered rings are described, along with their thermal reactivities and those of the corresponding Cu(II) (Cu(tact1:1), Cu(tact1:2)) and Zn(II) (Zn(tact1:1), Zn(tact1:2)) complexes. These enediyne macrocyclic ligands are not benzannulated and thus exhibit thermal Bergman cyclization temperatures near 200 degrees C by differential scanning calorimetry (DSC). Moreover, the synthetic route allows incorporation of additional carbon atoms into the macrocycles which increases their conformational flexibilities and lowers their Bergman cyclization temperatures. Specifically, as the size of the macrocycle increases, the temperatures at which these compounds undergo Bergman cyclization decrease by approximately 5 degrees C per additional carbon atom, leading to an overall decrease across the series of 19 degrees C. Incorporation of Cu(II) and Zn(II) into these macrocycles further reduces their cyclization temperatures relative to those of the free ligands. More uniquely, for Cu(tact1:1) and Zn(tact1:1), the observed cyclization temperatures vary by 27 degrees C with the Zn(II) complex lying to higher temperature (Cu(tact1:1) = 121 degrees C, (Zn(tact1:1) = 148 degrees C). As the macrocycle size is increased, the decrease in the Bergman cyclization temperatures observed for the free ligands does not systematically hold for the Cu(II) and Zn(II) derivatives. Rather, the Cu(II) complex exhibits the expected 9 degrees C decrease in the cyclization temperature (Cu(tact1:2) = 112 degrees C), whereas the temperature for the Zn(II) analogue increases by 15 degrees C (Zn(tact1:2) = 163 degrees C). From the X-ray crystal structure of the free ligand and the geometric structural preferences of the electronic configurations of Cu(II) and Zn(II), the higher cyclization temperatures for the Zn(II) complex with the larger ring size can be explained by a distortion of the macrocycle toward a more tetrahedral metal center geometry.

Chemical Phenomena↗
PubMed2001

Synthesis, isolation, and characterization of trisodium tricarbonyliridate (3-), Na3[Ir(CO)3]. Initial studies on its derivative chemistry and structural characterizations of trans-[Ir(CO)3(EPh3)2](-), E = Ge, Sn, and trans-[Co(CO)3(SnPh3)2](-1).

Reduction of Na[Ir(CO)4] by sodium metal in (Me2N)3PO, followed by treatment with liquid ammonia, provided high yields (ca. 90%) of unsolvated Na3[Ir(CO)3], a thermally stable, pyrophoric orange solid. This substance contains iridium in its lowest known formal oxidation state of -3 and has been characterized by IR spectroscopy, elemental analyses, and derivative chemistry, i.e., by its conversion to the triphenylgermyl and triphenylstannyl complexes, trans-[Ir(CO)3(EPh3)2](-), E = Ge, Sn. Single-crystal X-ray structures of the tetraethylammonium salts of these species, as well as [Co(CO)3(SnPh3)2](-), confirm the trigonal bipyramidal nature of the anions, originally predicted on the basis of their IR spectra in the carbonyl stretching frequency region. These structural characterizations provide important additional evidence for the presence of metal tricarbonyl units in Na3[M(CO)3], M = Co, Ir.

Journal Article↗
PubMed2001

Benzo[2,1-c:3,4-c']bis(1,2,3-thiaselenazole) (BSe) and its charge trasfer chemistry. Crystal and electronic structure of [BSe]3[ClO4]2.

The S-Se-N-based heterocycle benzo[2,1-c:3,4-c']bis(1,2,3-thiaselenazole) (BSe) can be prepared by the condensation of 1,4-diaminobenzene-2,3-dithiol with selenium tetrachloride. Crystals of this compound are not isomorphous with the related benzo[2,1-c:3,4-c']bis(1,2,3-dithiazole) (BT); a structure is adopted that allows for more extensive intermolecular Se- - -Se contacts. Electro-oxidation of BSe in the presence of [n-Bu4N][ClO4] affords metallic green needles of the charge transfer salt [BSe]3[ClO4]2, which exhibit a pressed pellet conductivity sigma(RT) = 10(-1) S cm(-1). The crystal structure of [BSe]3[ClO4]2 consists of slipped pi-stacks based on the triple-decker closed shell [BSe]3(2+) building block. The packing is analogous to that found for the charge transfer salt [BT]3[FSO3]2, for which sigma(RT) = 10(-2) S cm(-1). Extended Hückel band structure calculations on these two (sulfur- and selenium-based) 3:2 salts reveal more extensive intermolecular interactions in the selenium compound. As a result, the latter has a more two-dimensional electronic structure. Crystal data for Se2S2N2C6H2, a = 4.103(2) A, b = 12.159(2) A, c = 16.171(2) A, orthorhombic, Pbnm, Z = 4. Crystal data for Se6S6N6C18H6Cl2O4, a =17.00(1) A, b = 18.36(1) A, c = 10.679(4) A, 110.27(3), monoclinic, C2/c, Z = 4.

Journal Article↗
PubMed2001

Variable-temperature x-ray structural investigation of [Fe[HC(3,5-Me2pz)3]2](BF4)2 (pz= pyrazolyl ring): observation of a thermally induced spin state change from all high spin to an equal high spin-low spin mixture, concomitant with the onset of nonmerohedral twinning.

The complex [Fe[HC(3,5-Me(2)pz)(3)](2)](BF(4))(2) (pz = pyrazolyl ring) undergoes a phase transition that occurs concomitantly with a thermally induced spin conversion between the high-spin (HS, S = 2) and low-spin (LS, S = 0) states. Above 204 K the compound is completely HS with the structure in the C2/c space group with Z = 4. A crystal structure determination of this phase was performed at 220 K yielding the cell constants a = 20.338(2) A, b = 10.332(1) A, c = 19.644(2) A, beta = 111.097(2) degrees, and V = 3851.5(6) A(3). There is one unique iron(II) site at this temperature. Below 206 K the compound converts to a 50:50 mixture of HS and LS. The radical change in the coordination sphere for half of the iron(II) sites, most notably a shortening of the Fe-N bond distances by ca. 0.2 A, that accompanies this magnetic transition causes a phase transition. The crystal system changes from C-centered monoclinic to primitive triclinic with Z = 2 with two half-molecules on independent inversion centers. A crystal structure determination was performed at 173 K in space group P1 with a = 10.287(2) A, b = 11.355(3) A, c = 18.949(4) A, alpha = 90.852(4) degrees, beta = 105.245(4) degrees, gamma = 116.304(4) degrees, and V = 1892.3(8) A(3). All specimens investigated below the phase transition temperature were determined to be nonmerohedral twins. Temperature cycling between these two forms does not appear to degrade crystal quality. Previous magnetic susceptibility measurements indicate a second, irreversible increase in the magnetic moment the first time the crystals are cooled below 85 K. A crystal structure determination at 220 K of a specimen precooled to 78 K was not significantly different from those not cooled below 220 K.

Journal Article↗
PubMed2001

Gallane complexes with amido-amine ligands.

Gallane complexes bearing amido-amine ligands -N(R)CH2CMe2CH2NMe2 [R = H or SiMe3 (TMS)], (H2Ga[N(H)CH2CMe2CH2NMe2])2, 1, H2Ga[N(TMS)CH2CMe2CH2NMe2], 2, (H(Cl)Ga[N(H)CH2CMe2CH2NMe2])2, 3, ([(TMS)2N](H)Ga[N(H)CH2CMe2CH2NMe2])2, 4, and HGa[N(TMS)CH2CMe2CH2NMe2]2, 5, were synthesized from the reactions of the quinuclidine adducts of mono- and dichlorogallane with the corresponding lithium amides. Structural determinations of compounds 1, 3, and 4 showed all were dimeric with bridging amido groups. Rather than bond to gallium the tertiary amine groups in 1 and 4 were hydrogen-bonded to the amino N-H. In the structure of compound 3 the amine group occupied an axial position in the trigonal bipyramidal geometry of the five-coordinate gallium. The results were rationalized in terms of the steric and electronic properties of gallium ligands.

Journal Article↗
PubMed2001

Bradykinin modulation of tumor vasculature: I. Activation of B2 receptors increases delivery of chemotherapeutic agents into solid peripheral tumors, enhancing their efficacy.

Delivery of chemotherapeutic agents to solid peripheral tumors is compromised because the impaired microvasculature within and surrounding tumors limits diffusion and convection of agents from the vasculature to the tumor. Using a variety of rat tumor models, we show that intravenous administration of a vasoactive bradykinin B2 receptor agonist (Cereport, or labradimil; formerly RMP-7) enhances by nearly 3 times the delivery of the chemotherapeutic agent carboplatin, as well as the larger 70-kDa marker dextran, into ectopic and orthotopic solid tumors. This effect was selective for tumor tissue, with little or no increase seen in nontumor tissues and organs. Additionally, the increased carboplatin levels observed in tumors persisted for at least 90 min (the longest time point measured). In contrast to the consistent effects with hydrophilic compounds, delivery of the lipophilic, high protein-binding chemotherapeutics paclitaxel and 1,3-bis[2-chloroethyl]-1-nitrourea (BNCU) was not enhanced. Administration of Cereport with either carboplatin or another hydrophilic chemotherapeutic agent, doxorubicin, significantly increased efficacy of both agents, manifested by suppression of tumor growth and prolonged survival in tumor-bearing rats. These data demonstrate that delivery of chemotherapeutics to tumors can be pharmacologically increased (by stimulating bradykinin B2 receptors) without increasing the systemic exposure, or therefore, the toxic liability associated with higher chemotherapeutic doses.

Animals↗
PubMed2001

Bradykinin modulation of tumor vasculature: II. activation of nitric oxide and phospholipase A2/prostaglandin signaling pathways synergistically modifies vascular physiology and morphology to enhance delivery of chemotherapeutic agents to tumors.

Intravenous infusions of the bradykinin agonist Cereport (labradimil, formerly RMP-7) enhance delivery of concomitantly administered hydrophilic chemotherapeutic agents to solid tumors. The enhanced delivery produces greater in vivo efficacy of chemotherapeutic agents, manifested as suppressed tumor growth and increased survival in tumor-bearing rats. Here we elucidate the mechanisms of action involved with this unique phenomenon, at both the physical and biochemical levels. At the physical level we demonstrate that Cereport modifies the tumor vasculature in several important ways, including transient 1) reductions in interstitial fluid pressure within the tumor, 2) increases in pore size of the vasculature, and 3) increases in total vascular surface area. All three of these changes modify tumor-specific characteristics of the vasculature known to impede drug delivery to the tumor interstitium. Biochemically, we demonstrate that the activation of both of bradykinin's major signaling pathways, the nitric oxide and phospholipase A2/prostaglandin E2 are necessary events. Although pharmacologically blocking either pathway greatly reduced the effects of Cereport, stimulation of either pathway alone did not enhance delivery. However, simultaneous stimulation of both pathways (without exogenous bradykinin B2 receptor stimulation) produced a nearly 2-fold increase in delivery of carboplatin to the tumor. Thus, stimulation of endogenous bradykinin B2 receptors induces at least two parallel biochemical cascades that act synergistically to uniquely modify the tumor vasculature in ways that increase delivery and efficacy of chemotherapeutic agents.

Algorithms↗
PubMed2000

The first noncoordinated phosphonium diylide, [Me2P(C13H8)2]-, and its ylidic and cationic counterparts: synthesis, structural characterization, and interaction with the heavy group 2 metals.

Treatment of potassium or lithium fluorenide with MePCl2 generates the organophosphine MeP(C13H9)2, which on reaction with methyl iodide produces the phosphonium species [Me2P(C13H9)2]I in 74% yield. In the solid state, H...I contacts of < 3.3 A help generate a layered structure in which the fluorenyl rings are nearly parallel. On subsequent reaction of [Me2P(C13H9)2]I with either KH or K[N(SiMe3)2], the corresponding neutral phosphoylide, Me2P(C13H9)(C13H8), forms in 67% yield and was structurally characterized. The phosphonium iodide [Me2P(C13H9)2]I was allowed to react with Ae[N(SiMe3)2]2 (Ae = Ca, Ba), and the product from the reaction with the calcium complex was structurally identified as the salt [CaI(thf)5][Me2P(C13H8)2]. The anion, which is outside the coordination sphere of the calcium, represents the first structurally authenticated example of a free phosphonium diylide. The P-C(ylidic) bond length of 1.748(4) A reflects some partial multiple bond character. 1H and 31P NMR spectra suggest that the barium analogue is similar. Density functional theory calculations were performed on representative phosphonium diylides as an aid to interpreting the bonding in this class of compounds. Despite the strong electrostatic attraction that usually drives metal-ligand binding in highly ionic systems, calcium and barium prefer to coordinate to a single iodide ion and several neutral oxygen donors rather than to the charged diylide.

Journal Article↗
PubMed2000

Seven-coordinate [ReVON4X2]+ complexes (X = O and Cl).

The oxorhenium(V) complexes with ligands containing N4 (H2pmen) and N4O2 (H2bbpen, H2Clbbpen, and H2bped) donor atom sets have been synthesized. X-ray crystallographic analyses of the [ReO(H2pmen)Cl2]+, [ReO(bbpen)]+, and [ReO(bped)]+ complexes showed that all three cations share a rare seven-coordinate structure with a distorted pentagonal bipyramidal geometry, which represents a novel and potentially general structural motif in ReV = O complexes. 1H NMR spectroscopy shows that the structures of the complexes are retained in the solution.

Crystallography, X-Ray↗
PubMed2000

Formation of 1,10-disubstituted benzo

The first 1,10-heterodisubstituted benzo[c]cinnoline derivative 1 was prepared from the trinitrobiphenyl 2. Investigation of the mechanism of ring closure in 2, 5, and 8 revealed a complex reduction-oxidation-cyclization sequence. The mechanism is discussed in light of the stereoelectronic demands of the substituent functionalities. Benzo[c]cinnoline derivative 1 [C15H15N3S, monoclinic, P2(1)/c: a = 7.4063(3) A, b = 10.3739(5) A, c = 16.7642(8) A, beta = 91.816(1) degrees, Z = 4] and its 5-N-oxide 7(N5) [C18H18N3OS, triclinic, Pi: a = 8.1510(7) A, b = 8.6106(7) A, c = 12.102(1) A, alpha = 86.262(1) degrees, beta = 83.364(1) degrees, gamma = 74.711(1) degrees, Z = 4] were structurally characterized and showed a significant helical distortion of the heterocyclic ring. Oxidation of 1 with NCS or triamine 12 with PhI(OAc)2 led to a new heterocyclic ring system, ylide 13. Both benzo[c]cinnoline 1 and ylide 13 were characterized spectroscopically and the absorption spectra were correlated with the results of ZINDO calculations.

Journal Article↗
PubMed2000

Coaggregation of paramagnetic d- and f-block metal ions with a podand-framework amine phenol ligand.

This report covers initial studies in the coaggregation of nickel (Ni2+) and lanthanide (Ln3+) metal ions to form complexes with interesting structural and magnetic properties. The tripodal amine phenol ligand H3tam (1,1,1-tris(((2-hydroxybenzyl)amino)methyl)ethane) is shown to be particularly accommodating with respect to the geometric constraints of both transition and lanthanide metal ions, forming isolable complexes with both of these ion types. In the solid-state structure of [Ni(H2tam)(CH3CN)]PF6.2.5CH3CN.0.5CH3OH (1), the Ni(II) center has a distorted octahedral geometry, with an N3O2 donor set from the [H2tam]- ligand and a coordinated solvent (acetonitrile) occupying the sixth site. The reaction of stoichiometric amounts of H3tam with the Ni(II) ion in the presence of lanthanide(III) ions provides [LnNi2(tam)2]+ cationic complexes which contain coaggregated metal ions. These complexes are isolable and have been characterized by a variety of analytical techniques, with mass spectrometry proving to be particularly diagnostic. The solid-state structures of [LaNi2(tam)2(CH3OH)1/2(CH3CH2OH)1/2(H2O)]ClO4.0.5CH3OH.0.5CH3CH2OH.4H2O (2), [DyNi2(tam)2(CH3OH)(H2O)]ClO4.CH3OH. H2O(6), and [YbNi2(tam)2(H2O)]ClO4.2.58H2O(9) have been determined. Each complex contains two octahedral Ni(II) ions, each of which is encapsulated by the ligand tam3- in an N3O3 coordination sphere; each [Ni(tam)]-unit caps the lanthanide(III) ion via bridging phenoxy oxygen donor atoms. In 2, La3+ is eight-coordinated, while in 6, Dy(III) is seven- (to "weakly eight-") coordinated, and Yb(III) in 9 has a six-coordination environment. The complexes are symmetrically different, 2 possessing C2 symmetry and 6 and 9 having C1 symmetry. Magnetic studies of 2, 6, and 9 indicate that antiferromagnetic exchange coupling between the Ni(II) and Ln(III) ions increases with decreasing ionic radius of Ln(III).

Amines↗
PubMed2000

Intravenous cereport (RMP-7) enhances delivery of hydrophilic chemotherapeutics and increases survival in rats with metastatic tumors in the brain.

PURPOSE: The following experiments determined whether intravenous infusions of Cereport enhance delivery of chemotherapeutics and prolong survival in rats with metastatic tumors in the brain. METHODS: Autoradiography and scintillation were used to examine uptake of the lipophilic (paclitaxel and carmustine) and the hydrophilic (carboplatin) chemotherapeutic agents, as well as the large hydrophilic marker, 70 kDa dextran. Cereport was also tested in combination with the chemotherapeutic drugs carboplatin, vinorelbine, gemcitabine and carmustine to determine if Cereport could enhance the survival benefit beyond that provided by chemotherapy alone. RESULTS: Cereport enhanced the uptake of carboplatin and dextran, but not paclitaxel or carmustine. The pattern of Cereport's uptake effect with carboplatin revealed that Cereport selectively increased the proportion of highly permeable regions. Survival was significantly enhanced when Cereport was combined with either carboplatin, vinorelbine, or gemcitabine, but not carmustine, compared to each chemotherapeutic agent alone. CONCLUSIONS: These data provide the first evidence that Cereport, or any receptor-mediated approach intended to enhance the permeability of the blood-brain tumor barrier, can increase the delivery hydrophilic drugs to metastatic tumors in the brain, increasing survival in tumor-bearing rats.

Animals↗
PubMed2000

2,4,6-Trichlorophenylisonitrile and 2,4,6-trichlorobenzonitrile

The molecular structures of the title compounds, 2,4, 6-trichlorophenylisonitrile (IUPAC name: 2,4,6-trichlorophenyl isocyanide), C(7)H(2)Cl(3)N, and 2,4,6-trichlorobenzonitrile, C(7)H(2)Cl(3)N, are normal. The two structures are not isomorphous, but do contain similar two-dimensional layers in which pairs of molecules are held together by pairs of Cl.CN [3.245 (3) A] or Cl.NC [3.153 (2) A] interactions. The two-dimensional isomorphism is lost through different layer-stacking modes.

Journal Article↗
PubMed1999

Enhanced delivery of carboplatin into brain tumours with intravenous Cereport (RMP-7): dramatic differences and insight gained from dosing parameters.

Cereport (RMP-7) is a selective bradykinin B2 receptor agonist which increases the permeability of the 'blood-brain tumour barrier' (BBTB) to increase delivery of chemotherapeutic agents to brain tumours. A series of experiments was performed in an RG2 rodent model of glioma to evaluate and refine intravenous (i.v.) parameters to optimize Cereport's clinical utility. The first experiment demonstrated that while carboplatin levels were increased by twofold when given as a bolus during the Cereport infusion, no increase in carboplatin levels were seen when Cereport and carboplatin were simultaneously co-infused for 15 min. A subsequent experiment established that a major factor responsible for the lack of an effect with the co-infusion paradigm was tachyphylaxis to Cereport during the 15 min infusion, for a progressively diminished response to Cereport occurred over that time frame, as plasma levels of carboplatin were rising. A final experiment adjusted the timing of the Cereport and carboplatin infusions so that higher plasma carboplatin levels were achieved prior to initiating the Cereport infusion. Significant uptake effects were achieved when the carboplatin infusion preceded the Cereport infusion by 10 min (i.e. 5 min overlap in the delivery of the two agents). Collectively, these data provide the first systematic evaluation of dosing parameters involving receptor-mediated changes in BBTB permeability and provide new information regarding the pharmacodynamics and potential clinical use of Cereport.

Animals↗
PubMed1998

Central analgesic actions of loperamide following transient permeation of the blood brain barrier with Cereport (RMP-7).

The bradykinin analog, Cereport (RMP-7), was designed to increase permeability of the blood brain barrier (BBB). Over the past several years it has been developed primarily as a means of increasing permeability of the blood brain tumor barrier, where early evidence indicated a particularly robust and reliable effect. The present series of experiments were intended to determine whether Cereport might also be used to increase delivery of pharmacological agents across the normal (i.e., non-tumor) BBB. This was accomplished by testing the ability of Cereport to enhance delivery of the peripherally acting opiate agonist, loperamide, to the brain, as evidenced by induction of a centrally mediated analgesic effect. Intravenous administration of a combination of Cereport and loperamide produced a significant analgesic effect (2-fold increase in response times) when animals were tested on a hotplate apparatus. Loperamide alone did not produce analgesia. An analysis of the time course of analgesia revealed a graded onset of analgesia which peaked at 30 min, maintained asymptote at 60 min, and began to diminish by 120 min following Cereport and loperamide administration. Finally, the analgesic effects of combining Cereport and loperamide were completely blocked when animals were pre-treated with the opiate antagonist naloxone, demonstrating that the analgesia was mediated through opiate receptors. Collectively, these results suggest that Cereport was able to increase delivery of loperamide across the BBB, allowing it to gain access to opiate receptors in the CNS to produce a centrally mediated analgesic effect. They therefore provide clear evidence that safe and well-tolerated doses of Cereport can increase permeability of the normal (i.e., non-tumor) BBB. Moreover, they provide the first evidence of a pharmacological effect specifically enabled by controlled (i.e., receptor-mediated) modulation of the BBB.

Analgesics↗
PubMed1995

Comparison of shoulder injury in collegiate- and master's-level swimmers.

The need to investigate shoulder injury in swimmers other than the young and elite is evident, as all ages and levels are represented in the 100 million Americans who classify themselves as swimmers. To investigate the differences between young, highly competitive collegiate swimmers and older, less elite swimmers, a survey questionnaire was distributed to 100 collegiate and 100 master's swim teams. Questions regarding swimming routines, performance standards, and several possible predisposing factors associated with "swimmer's shoulder," as implicated in the literature, were investigated. As expected, the results revealed that the collegiate group swam the higher yardage, with considerably faster times in both the 50- and the 1,000-yd freestyle, and more than double the number of workouts per week. However, the collegiate and master's group reported similar percentages, 47 and 48%, respectively, experiencing shoulder pain lasting 3 weeks or more, despite the lesser distances and intensities associated with the latter group. Chi-square analysis revealed no association between shoulder pain and perceived level of flexibility, hand paddle usage, or breathing side for either group. However, over 50% of the swimmers with shoulder pain in both groups perceived that increased intensities and/or distance provoked shoulder pain, indicating that fatigue may be the issue to avoid and on which to focus. Strengthening the muscles of the shoulder, specifically those shown to have a propensity to fatigue, provides a strong defense against injury, as fatigue of the shoulder muscles may be the initial antecedent to swimmer's shoulder. These results give the swimmer, coach, and medical practitioner feedback to consider for a swimmer of any age or level.

Adult↗