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- Ekelund, Mats
(author)
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Competition and innovation in the Swedish pharmaceutical market
- 2001
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Doctoral thesis (other academic/artistic)abstract
- This thesis consists of four essays in economics related to the pharmaceutical market. The first essay, Pharmaceutical Pricing in a Regulated Market, compares the pricing of new pharmaceuticals in the Swedish market where prices are regulated, with the results of Lu and Comanor who studied the pricing of new pharmaceuticals in the US market. The results indicate that price regulation discourages the use of penetration strategies and decreases price competition between brand name drugs. The second essay, Innovativeness and Market Shares in the Pharmaceutical Industry, analyzes the pharmaceutical market in a model of horizontal and vertical product differentiation. The implications from the model are tested on data from the Swedish pharmaceutical market. Vertically differentiated drugs are found to gain larger market shares, command higher prices, and be less sensitive to substitutes than drugs that are only horizontally differentiated. The third essay, Generic entry before and after reference prices, examines the effect of the reference pricing system on generic entry in markets where brand name pharmaceuticals lose patent protection. The main result is that savings due to increased competition in markets affected by the reference pricing system may have been outbalanced by higher prices due to less competition in markets where the reference pricing system led to deterred entry. The fourth essay, Innovative Drugs and the Increase in Pharmaceutical Expenditures, seeks to establish the most important factors behind the growth in pharmaceutical expenditures. One important conjecture is that the change in the drug price index has little impact on the rate at which pharmaceutical expenditures grow. Instead, the introduction of new innovative drugs seems to be the most important driving force of the growth in pharmaceutical expenditures.
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| 2. |
- Ekelund, Mats
(author)
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Generic entry before and after reference prices
- 2001
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Other publication (other academic/artistic)abstract
- This paper studies the effect of the reference pricing system on generic entry in markets where brand name pharmaceuticals lose patent protection. I find the likelihood of generic entry after patent expiration to decrease, after the introduction of the reference pricing system. According to my estimates savings due to increased competition in markets affected by the reference pricing system may have been outbalanced by higher prices, due to less competition in markets where the reference pricing system led to deterred entry.
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| 3. |
- Ekelund, Mats
(author)
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Innovative Drugs and the Increase in Pharmaceutical Expenditures
- 2001
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Other publication (other academic/artistic)abstract
- This paper investigates how the growth in pharmaceutical expenditures is determined. A theoretical model of the growth in pharmaceutical expenditures is analyzed and the impact of new innovative drugs on the growth of Swedish pharmaceutical expenditures is studied empirically. The result from the theoretical model is that the potential driving forces of the steady state growth in expenditures are inflation in introductory drug prices, the inflow of new innovative drugs and the increase in the underlying demand. The result from the empirical study is that introductory drug prices have,been stable durin'g this period but that new innovative drugs have opened up new markets and increased the drug consumption. An important conclusion is that the change in the drug price index is of little importance for the growth in pharmaceutical expenditures in steady state. At present, it might be necessary to reduce the access to new innovative drugs if the steady state growth rate is to be reduced.
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| 4. |
- Liu, Q, et al.
(author)
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Administration of Lactobacillus plantarum 299v reduces side-effects of external radiation on colon anastomotic healing in an experimental model
- 2001
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In: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 3:4, s. 245-252
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Preoperative radiotherapy of patients with rectal carcinoma is frequently used to reduce the incidence of local recurrence. However, the radiation therapy is associated with several complications, including diarrhea, retarded anastomotic healing and mucosal atrophy. Exogenous administration of lactobacilli has been demonstrated to be effective in stimulating intestinal mucosal growth and reduce mucosal inflammation. The objective of this study was to examine the effects of Lactobacillus plantarum 299v administration on external radiation injury in colon anastomotic healing at different time points. MATERIAL AND METHODS: Sprague-Dawley rats were treated with Lb. plantarum 299v or saline as control and received external radiation of the lower abdomen (10 Gy/day) on day 3 and 7 of the experiment. After 4 days, a colonic resection with anastomosis was performed. Animals were sacrificed on 4th, 7th and 11th day postoperatively. Body weight, white blood cell (WBC) count, mucosal myeloperoxidase (MPO) activity, hydroxyproline, nucleotide, DNA and RNA content, colonic bacterial microflora, bacterial translocation and histology were evaluated. RESULTS: On the 4th postoperative day body weight, WBC and MPO decreased significantly after radiation. On the 7th postoperative day MPO decreased after radiation. In the two irradiated groups it decreased significantly in the Lb. plantarum group compared to the radiated group without treatment. Collagen concentration on the 7th postoperative day was significantly higher in Lb. plantarum group without radiation compared to the group with radiation without Lb. plantarum. On the 11th postoperative day MPO was significantly higher in irradiated rats without treatment compared to Lb. plantarum treatment. The collagen concentration increased significantly in the irradiated Lb. plantarum group compared to the other two groups. CONCLUSION: The collagen content decreased and MPO activity increased significantly of the colonic anastomosis in irradiated rats without treatment compared to those treated with Lb. plantarum. It therefore seems that administration of Lactobacillus plantarum 299v reduces the intestinal injury and inflammation following external radiation and improves the colonic anastomotic healing.
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| 5. |
- Salehi, S Albert, et al.
(author)
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Total parenteral nutrition modulates hormone release by stimulating expression and activity of inducible nitric oxide synthase in rat pancreatic islets
- 2001
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In: Endocrine. - 1355-008X. ; 16:2, s. 97-104
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Journal article (peer-reviewed)abstract
- The expression and activities of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) in relation to insulin and glucagon secretory mechanisms were investigated in islets isolated from rats subjected to total parenteral nutrition (TPN) for 10 d. TPN is known to result in significantly increased levels of plasma lipids during the infusion time. In comparison with islets from freely fed control rats, islets taken from TPN rats at d 10 displayed a marked decrease in glucose-stimulated insulin release (4.65 +/- 0.45 ng/[islet x h] vs 10.25 +/- 0.65 for controls) (p < 0.001) accompanied by a strong iNOS activity (18.3 +/- 1.1 pmol of NO/[min x mg of protein]) and a modestly reduced cNOS activity (11.3 +/- 3.2 pmol of NO/[min x mg of protein] vs 17.7 +/- 1.7 for controls) (p < 0.01). Similarly, Western blots showed the expression of iNOS protein as well as a significant reduction in cNOS protein in islets from TPN-treated rats. The enhanced NO production, which is known to inhibit glucose-stimulated insulin release, was manifested as a strong increase in the cyclic guanosine 5'-monophosphate content in the islets of TPN-treated rats (1586 +/- 40 amol/islet vs 695 +/- 64 [p < 0.001] for controls). Moreover, the content of cyclic adenosine monophosphate (cAMP) was greatly increased in the TPN islets (80.4 +/- 2.1 fmol/islet vs 42.6 +/- 2.6 [p < 0.001] for controls). The decrease in glucose-stimulated insulin release was associated with an increase in the activity of the secretory pathway regulated by the cAMP system in the islets of TPN-treated rats, since the release of insulin stimulated by the phosphodiesterase inhibitor isobutylmethylxanthine was greatly increased both in vivo after iv injection and after in vitro incubation of isolated islets. By contrast, the release of glucagon was clearly reduced in islets taken from TPN-treated rats (33.5 +/- 1.5 pg/[islet x h] vs 45.5 +/- 2.2 for controls) (p < 0.01) when islets were incubated at low glucose (1.0 mmol/L). The data show that long-term TPN treatment in rats brings about impairment of glucose-stimulated insulin release, that might be explained by iNOS expression and a marked iNOS-derived NO production in the beta-cells. The release of glucagon, on the other hand, is probably decreased by a direct "nutrient effect" of the enhanced plasma lipids. The results also suggest that the islets of TPN-treated rats have developed compensatory insulin secretory mechanisms by increasing the activity of their beta-cell cAMP system.
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| 6. |
- Salehi, S Albert, et al.
(author)
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TPN-evoked dysfunction of islet lysosomal activity mediates impairment of glucose-stimulated insulin release
- 2001
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In: American Journal of Physiology: Endocrinology and Metabolism. - 1522-1555. ; 281:1, s. 171-179
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Journal article (peer-reviewed)abstract
- We examined the relation between nutrient-stimulated insulin secretion and the islet lysosome acid glucan-1,4-alpha-glucosidase system in rats undergoing total parenteral nutrition (TPN). During TPN treatment, serum glucose was normal, but free fatty acids, triglycerides, and cholesterol were elevated. Islets from TPN-infused rats showed increased basal insulin release, a normal insulin response to cholinergic stimulation but a greatly impaired response when stimulated by glucose or alpha-ketoisocaproic acid. This impairment of glucose-stimulated insulin release was only slightly ameliorated by the carnitine palmitoyltransferase 1 inhibitor etomoxir. However, in parallel with the impaired insulin response to glucose, islets from TPN-infused animals displayed reduced activities of islet lysosomal enzymes including the acid glucan-1,4-alpha-glucosidase, a putative key enzyme in nutrient-stimulated insulin release. By comparison, the same lysosomal enzymes were increased in liver tissue. Furthermore, in intact control islets, the pseudotetrasaccharide acarbose, a selective inhibitor of acid alpha-glucosidehydrolases, dose dependently suppressed islet acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase activities in parallel with an inhibitory action on glucose-stimulated insulin secretion. By contrast, when incubated with intact TPN islets, acarbose had no effect on either enzyme activity or glucose-induced insulin release. Moreover, when acarbose was added directly to TPN islet homogenates, the dose-response effect on the catalytic activity of the acid alpha-glucosidehydrolases was shifted to the right compared with control homogenates. We suggest that a general dysfunction of the islet lysosomal/vacuolar system and reduced catalytic activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase may be important defects behind the impairment of the transduction mechanisms for nutrient-stimulated insulin release in islets from TPN-infused rats.
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